bluuebunny/crossref_metadata_2025 huggingface dataset:
Optic neuropathy as an early manifestation of granulomatosis with polyangiitis: a case report and literature review
Authors: Kim Yukang , Woo Tonghoon , Lee Sun-Uk , Park Euyhyun , Shin Hyun-Jin , Sim Jongmin , Kim Gerard Jounghyun , Kim Ji-Soo
Published: February 2025

Introduction

Ophthalmic involvement occurs in up to 40% of patients with granulomatosis with polyangiitis (GPA), usually confined to the anterior segment. Herein, we describe patients presenting with optic neuropathy as an early manifestation of GPA, without other signs of ocular or adnexa involvement.

Methods

We report a case of isolated optic neuropathy without other ocular or adnexal involvement and examine the reported clinical features of 17 additional patients through a literature review. We analyzed clinical characteristics and neuro-ophthalmological findings and discuss the clinical implications for the early detection of GPA-associated optic neuropathy.

Results

Among the 17 patients, 10 had optic neuropathy confined to one eye, three exhibited simultaneous bilateral optic neuropathies at initial presentation, and four had unilateral involvement initially; however, the fellow eye was subsequently affected during follow-up. Nine patients had optic neuropathy as the first clinical presentation and no prior diagnosis of GPA (9/17, 53%). Among the 21 eyes (15 patients, excluding two without descriptions), disc edema was observed in five eyes (24%). Visual impairment was often profound; the measurements of 23 affected eyes at the initial presentation showed that the patient’s acuity was to count fingers or worse (14/23, 61%). The final visual outcome was often poor, with significant visual recovery in only eight eyes (8/23, 35%). Other constitutional symptoms or systemic involvements were found in most patients (15/16, 94%), mostly affecting the lung (n = 10), sinus (n = 9), and pachymeninges (n = 8). Furthermore, 88% of the patients (15/17) showed positive results on antineutrophil cytoplastic antibody. Elevated CRP (n = 6) or ESR (n = 5) was found in 56% of cases.

Discussion

Our case and literature review indicates that optic neuropathy can present in the context of systemic inflammation of GPA, without any other signs of ocular or orbital involvement. Catching other clinical, imaging, and laboratory signs of systemic inflammation is important in cases of GPA-associated optic neuropathy with atypical presentations.
Evaluating the performance of ChatGPT in patient consultation and image-based preliminary diagnosis in thyroid eye disease
Authors: Wang Yue , Yang Shuo , Zeng Chengcheng , Xie Yingwei , Shen Ya , Li Jian , Huang Xiao , Wei Ruili , Chen Yuqing
Published: February 2025

Background

The emergence of Large Language Model (LLM) chatbots, such as ChatGPT, has great promise for enhancing healthcare practice. Online consultation, accurate pre-diagnosis, and clinical efforts are of fundamental importance for the patient-oriented management system.

Objective

This cross-sectional study aims to evaluate the performance of ChatGPT in inquiries across ophthalmic domains and to focus on Thyroid Eye Disease (TED) consultation and image-based preliminary diagnosis in a non-English language.

Methods

We obtained frequently consulted clinical inquiries from a published reference based on patient consultation data, titled A Comprehensive Collection of Thyroid Eye Disease Knowledge. Additionally, we collected facial and Computed Tomography (CT) images from 16 patients with a definitive diagnosis of TED. From 18 to 30 May 2024, inquiries about the TED consultation and preliminary diagnosis were posed to ChatGPT using a new chat for each question. Responses to questions from ChatGPT-4, 4o, and an experienced ocular professor were compiled into three questionnaires, which were evaluated by patients and ophthalmologists on four dimensions: accuracy, comprehensiveness, conciseness, and satisfaction. The preliminary diagnosis of TED was deemed accurate, and the differences in the accuracy rates were further calculated.

Results

For common TED consultation questions, ChatGPT-4o delivered more accurate information with logical consistency, adhering to a structured format of disease definition, detailed sections, and summarized conclusions. Notably, the answers generated by ChatGPT-4o were rated higher than those of ChatGPT-4 and the professor, with accuracy (4.33 [0.69]), comprehensiveness (4.17 [0.75]), conciseness (4.12 [0.77]), and satisfaction (4.28 [0.70]). The characteristics of the evaluators, the response variables, and other quality scores were all correlated with overall satisfaction levels. Based on several facial images, ChatGPT-4 twice failed to make diagnoses because of lacking characteristic symptoms or a complete medical history, whereas ChatGPT-4o accurately identified the pathologic conditions in 31.25% of cases (95% confidence interval, CI: 11.02–58.66%). Furthermore, in combination with CT images, ChatGPT-4o performed comparably to the professor in terms of diagnosis accuracy (87.5, 95% CI 61.65–98.45%).

Conclusion

ChatGPT-4o excelled in comprehensive and satisfactory patient consultation and imaging interpretation, indicating the potential to improve clinical practice efficiency. However, limitations in disinformation management and legal permissions remain major concerns, which require further investigation in clinical practice.
An overview of current phase 3 radiopharmaceutical therapy clinical trials
Authors: Lepareur Nicolas
Published: February 2025

Over the past few years, radiopharmaceutical therapy has emerged as a groundbreaking therapeutic modality, taking advantage of the unique properties of radionuclides to deliver molecularly targeted therapy with high precision and transforming the landscape of precision oncology and personalized medicine. Its development reflects decades of advances in nuclear medicine, chemistry, and cancer biology. However, until recently, definitive clinical evidence was lacking to establish it into treatment plans, with few large randomized controlled clinical studies. The last two decades witnessed a paradigm shift, with three successful phase 3 studies which shed light on radiopharmaceutical therapy. This paper offers a brief overview of currently active phase 3 studies to highlight the dynamism and promise of this clinical domain, as well as the large variety of cancers being treated.
Age-related changes in neural oscillations vary as a function of brain region and frequency band
Authors: Park Jinhan , Ho Rachel L. M. , Wang Wei-en , Chiu Shannon Y. , Shin Young Seon , Coombes Stephen A.
Published: February 2025

Advanced aging is associated with robust changes in neural activity. In addition to the well-established age-related slowing of the peak alpha frequency, there is a growing body of evidence showing that older age is also associated with changes in alpha power and beta power. Despite the important progress that has been made, the interacting effects of age and frequency band have not been directly tested in sensor and source space while controlling for aperiodic components. In the current study we address these limitations. We recruited 54 healthy younger and older adults and measured neural oscillations using a high-density electroencephalogram (EEG) system during resting-state with eyes closed. After preprocessing the EEG data and controlling for aperiodic components, we computed alpha and beta power in both sensor and source space. Permutation two-way ANOVAs between frequency band and age group were performed across all electrodes and across all dipoles. Our findings revealed significant interactions in sensorimotor, parietal, and occipital regions. The pattern driving the interaction varied across regions, with older age associated with a progressive decrease in alpha power and a progressive increase in beta power from parietal to sensorimotor regions. Our findings demonstrate that age-related changes in neural oscillations vary as a function of brain region and frequency band. We interpret our findings in the context of clinical and preclinical evidence of age effects on the cholinergic circuit and the Cortico-Basal Ganglia-Thalamo-Cortical (CBGTC) circuit.
Associations of the Life’s Essential 8 with Parkinson’s disease: a population-based study
Authors: Zhou Chenguang , Cheng Oumei
Published: February 2025

Background

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with increasing global prevalence. This study investigated the association between the American Heart Association’s Life’s Essential 8 (LE8) and PD prevalence using a large, nationally representative database.

Methods

We analyzed data from 18,277 participants aged 40 years and older from the National Health and Nutrition Examination Survey (NHANES) 2005–2018. LE8 scores were calculated based on diet, physical activity, nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure. PD cases were identified through self-reported anti-PD medication use. Multivariate logistic regression models were employed to examine the association between LE8 and PD prevalence, adjusting for various demographic and clinical factors. In addition, we performed restricted cubic splines (RCS), subgroup analyses, and weighted quantile sum (WQS) regression to verify the robustness of the study results.

Results

The prevalence of PD was 1.3% in the study population. After full adjustment, individuals with moderate (50–79) and high (80–100) LE8 scores showed lower odds of PD compared to those with low (0–49) scores (OR 0.53, 95% CI 0.29–0.97 and OR 0.43, 95% CI 0.17–1.04, respectively; p for trend <0.05). A dose-response relationship was observed between LE8 scores and PD prevalence. WQS regression identified dietary factors and glycemic health as the main contributors to the inverse association between LE8 and PD.

Conclusion

Our findings suggest a significant inverse association between Life’s Essential 8 (LE8) and PD prevalence, with dietary factors and glycemic health emerging as the most influential components.
Efficacy of vigorous physical activity as an intervention for mitigating depressive symptoms in adolescents and young adults: a comprehensive systematic review and meta-analysis
Authors: Yang Wei , Chen Huijing , Liu Wei , Qu Sheng , Ge Yao , Song Jin
Published: February 2025

Purpose

This study aimed to evaluate the effectiveness of vigorous physical activity as an intervention for alleviating depressive symptoms among adolescents and young adults.

Methods

A comprehensive search on systematically reliable databases was carried out, and studies running till August 2023 were considered in this study. The articles included in this meta-analysis assessed the impact of exercise interventions on depressive symptomatology in adolescents and young adults. Two independent investigators screened the studies, extracted data, and evaluated quality.

Results

Physical activity produced an important reduction in depressive symptoms [SMD] = −4.23, 95% CI: −7.02, −1.44, p = 0.0001; a moderate effect size in both the adolescent population with clinical depression and adolescents who presented with subclinical depressive symptoms. Notably, vigorous physical exercise worked most favorably for adolescent depressive symptomatology, while moderate-intensity exercise was the best choice for adolescents with diagnosed clinical depression.

Conclusion

This meta-analysis suggests that vigorous physical activity could reduce depressive symptoms in adolescents and young adults. However, further studies are needed to provide clearer recommendations regarding the type, duration, and intensity of exercise necessary to treat clinical depression in this population.
Artificial intelligence and pediatric acute kidney injury: a mini-review and white paper
Authors: Hu Jieji , Raina Rupesh
Published: February 2025

Acute kidney injury (AKI) in pediatric and neonatal populations poses significant diagnostic and management challenges, with delayed detection contributing to long-term complications such as hypertension and chronic kidney disease. Recent advancements in artificial intelligence (AI) offer new avenues for early detection, risk stratification, and personalized care. This paper explores the application of AI models, including supervised and unsupervised machine learning, in predicting AKI, improving clinical decision-making, and identifying subphenotypes that respond differently to interventions. It discusses the integration of AI with existing risk scores and biomarkers to enhance predictive accuracy and its potential to revolutionize pediatric nephrology. However, barriers such as data quality, algorithmic bias, and the need for transparent and ethical implementation are critical considerations. Future directions emphasize incorporating biomarkers, expanding external validation, and ensuring equitable access to optimize outcomes in pediatric AKI care.
Dezocine modulates the reinstatement of conditioned place preference in morphine-dependent rats via the dopamine reward circuitry
Authors: He Yan , Piao Zhi-Sheng , Jia Yi , Wu Hui-Qi , Wang Xiao-Qiang , Yu Wei-Feng , Wu Fei-Xiang
Published: February 2025

Introduction

Opioid addiction is a significant public health issue, with existing treatments such as buprenorphine and methadone exhibiting limitations, including side effects and insufficient prevention of relapse. Novel therapeutic strategies are needed to address these challenges. This study investigates the potential of dezocine in reducing addiction-related behaviors and preventing relapse.

Methods

A morphine-induced conditioned place preference (CPP) model was established in rats to evaluate the effect of dezocine on addiction-related behaviors. Behavioral assessments were conducted to measure withdrawal symptoms and CPP reinstatement. To explore the underlying mechanism, Western blot (WB) and immunofluorescence (IF) were used to quantify the expression of phosphorylated DARPP32 (p-DARPP32) and DOPA decarboxylase (DDC) in reward-related brain regions, including the nucleus accumbens (NAc), ventral tegmental area (VTA), hippocampus (HP), and prefrontal cortex (PFC).

Results

Dezocine significantly reduced withdrawal symptoms and prevented CPP reinstatement, indicating its potential to alleviate addiction behaviors. Western blotting and immunofluorescence analysis revealed that dezocine increased p-DARPP32 expression in the NAc, VTA, HP, and PFC, without altering DDC levels.

Discussion

These findings suggest that dezocine may exert its therapeutic effects by inhibiting kappa opioid receptor activation and enhancing dopamine signaling in reward-related brain circuitry. The increase in p-DARPP32 expression in key brain regions supports this mechanism, providing insights into the potential clinical application of dezocine for managing opioid addiction. Dezocine represents a promising candidate for opioid addiction treatment, with the ability to control withdrawal symptoms and prevent relapse.
Multi-omics revealed that the postbiotic of hawthorn-probiotic alleviated constipation caused by loperamide in elderly mice
Authors: Wei Yu , Chen Shuai , Ling Ying , Wang Wei , Huang Yali
Published: February 2025

Background

Constipation is a prevalent and recurrent gastrointestinal disorder causing significant discomfort. However, current treatments often prove ineffective. Previous research indicates that the postbiotic derived from a combination of hawthorn and probiotics can alleviate constipation. This study aimed to investigate its mechanisms using loperamide-induced constipation in aged KM mice.

Methods

Constipated mice were divided into groups receiving 10% lactulose (Y), hawthorn extract (S), probiotics (F), and the postbiotic of hawthorn-probiotic (FS). UPLC–MS metabolomics identified constituents of F, S, and FS. Network pharmacological analysis identified targets affected by FS. RT-qPCR assessed target expression in mouse colons, along with IL-6 and IL-17A levels. Molecular docking with AutoDock Tools1.5.6 evaluated interactions between FS components and targets. ex vivo colonic organ culture and RT-qPCR assessed target changes. Molecular dynamics analysis further scrutinized interactions. Targeted metabolomics measured short-chain fatty acid levels in mouse stool.

Results

UPLC–MS metabolomics revealed distinct profiles for F, S, and FS, with FS showing decreased toxic substances and increased beneficial ones compared to S. Network pharmacology identified 20 cross-targets of FS in constipation. RT-qPCR showed decreased NR1I2 and SULT1A1 and increased GLP-2r in FS-treated mice. Inflammatory cytokines IL-6 and IL-17A were also reduced. ex vivo colonic organ culture and molecular docking identified effective combinations such as TNF-Baicalin and AQP3-Quinacridone. RMSD, RMSF, and RG analyses indicated favorable interactions between small molecules and targets. Targeted metabolomics revealed differing short-chain fatty acid contents in feces among groups.

Conclusion

The postbiotic of hawthorn-probiotic alleviates constipation by regulating intestinal water and sodium metabolism, maintaining the intestinal barrier and gut flora, promoting epithelial cell proliferation, reducing inflammatory responses, and improving short-chain fatty acid metabolism.
Reclassification of variants of uncertain significance by race, ethnicity, and ancestry for patients at risk for breast cancer
Authors: Pleasant Versha , Boggan Jordyn , Richards Blair , Milliron Kara J. , Purrington Kristen S. , Simon Michael , Merajver Sofia
Published: February 2025

Introduction

Although most variants of uncertain significance (VUS) in breast cancer susceptibility genes are eventually downgraded to benign or likely benign in individuals of European ancestry, it is unclear if this also applies to non-European populations. This study examines the time to and type of VUS reclassification among a diverse cohort at risk for breast cancer.

Methods

A multicenter retrospective analysis examined people assigned female at birth (AFAB) who underwent genetic testing from 2013 to 2021 with VUS in ATM, BARD1, BRCA1/2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C/D, STK11, and/or TP53. Demographic data were collected [including race, ethnicity, and ancestry (REA)], as well as time to and type of reclassification. Frequency data and univariable and multivariable analyses were performed (p < 0.05 was considered statistically significant).

Results

There were 932 participants who had a total of 1,032 VUS (905 unique variants), with 20% who underwent reclassification of their results. The proportion of reclassified VUS among the largest represented REA groups was 19%, 23%, and 27% for White, Black or African American, and Asian people, respectively. REA was not associated with VUS reclassification (p = 0.25). The mean time to VUS reclassification was 2.8 years and was not significantly associated with REA (p = 0.16). Most VUS were downgraded to benign/likely benign (n = 187, 92%).

Discussion

Our findings demonstrate that REA is not significantly associated with VUS reclassification or time to reclassification, with the majority of VUS being downgraded across REA. This study allows for improved and more equitable genetic counseling. It may also provide more reassurance to those groups that may have a higher likelihood of VUS results.
Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review
Authors: Czarny Jakub , Galli Dominika , Wziątek Agnieszka , Pastorczak Agata , Szmyd Bartosz , Przybyszewski Borys , Raciborska Anna , Jończyk-Potoczna Katarzyna , Derwich Katarzyna
Published: February 2025

Germinal predisposition to malignancy is found in approximately 10% of oncological pediatric patients. As awareness of cancer risk factors associated with germline mutations increases, and with advancements in molecular techniques, more carefully selected patients are being tested. This approach enables the identification of new variants—both those that are clearly linked to tumorigenesis and candidates, which biological role needs to be functionally verified. Pathogenic variants within cancer-predisposing genes not only increase nearly eightfold the risk of secondary cancers but also may be associated with excessive toxicity of antineoplastic treatment. We present the case of a girl who developed classical Hodgkin lymphoma at the age of 8 years and secondary Ewing sarcoma at the age of 16 years. Her father was diagnosed with classical Hodgkin lymphoma at the age of 27 years. Genetic testing revealed the carriership of a germline heterozygous variant in the PALB2 gene (NM_024675.4:c.110G>A, p.Arg37His) in both the patient and her father. Since the patient was exposed to chemotherapy due to lymphoma prior to the development of secondary malignancy and the variant is classified as an aberration of unknown significance, the causative role of the PALB2 variant remains uncertain. Nevertheless, the presented case may indicate the possible interplay between inherited genetic predisposition and the exposure to cytostatic drugs, which both are involved in promoting secondary cancers in pediatric patients.
Identification of benign and malignant breast nodules on ultrasound: comparison of multiple deep learning models and model interpretation
Authors: Wen Xi , Tu Hao , Zhao Bingyang , Zhou Wenbo , Yang Zhuo , Li Lijuan
Published: February 2025

Background and Purpose

Deep learning (DL) algorithms generally require full supervision of annotating the region of interest (ROI), a process that is both labor-intensive and susceptible to bias. We aimed to develop a weakly supervised algorithm to differentiate between benign and malignant breast tumors in ultrasound images without image annotation.

Methods

We developed and validated the models using two publicly available datasets: breast ultrasound image (BUSI) and GDPH&SYSUCC breast ultrasound datasets. After removing the poor quality images, a total of 3049 images were included, divided into two classes: benign (N = 1320 images) and malignant (N = 1729 images). Weakly-supervised DL algorithms were implemented with four networks (DenseNet121, ResNet50, EffientNetb0, and Vision Transformer) and trained using 2136 unannotated breast ultrasound images. 609 and 304 images were used for validation and test sets, respectively. Diagnostic performances were calculated as the area under the receiver operating characteristic curve (AUC). Using the class activation map to interpret the prediction results of weakly supervised DL algorithms.

Results

The DenseNet121 model, utilizing complete image inputs without ROI annotations, demonstrated superior diagnostic performance in distinguishing between benign and malignant breast nodules when compared to ResNet50, EfficientNetb0, and Vision Transformer models. DenseNet121 achieved the highest AUC, with values of 0.94 on the validation set and 0.93 on the test set, significantly surpassing the performance of the other models across both datasets (all P < 0.05).

Conclusion

The weakly supervised DenseNet121 model developed in this study demonstrated feasibility for ultrasound diagnosis of breast tumor and showed good capabilities in differential diagnosis. This model may help radiologists, especially novice doctors, to improve the accuracy of breast tumor diagnosis using ultrasound.
Ivabradine in treatment of symptomatic heart failure and supraventricular tachycardias in patients under six months of age
Authors: Gómez-Ganda L. , Parramón-Teixidó C. J. , Giralt-García G. , Fernández-García C. , Ferrer-Menduiña Q. , Cabañas-Poy M. J.
Published: February 2025

Background

Although heart failure (HF) and supraventricular tachycardias (SVT) are associated with high morbidity and mortality in pediatrics, especially, in children under 6 months; the efficacy of available treatments is limited, requiring the use of off-label therapies. The aim of the study is to investigate the efficacy, dosage, and safety of off-label ivabradine in patients under 6 months of age with HF or SVT.

Methods

Retrospective observational study, which included patients under 6 months of age with HF or SVT who received ivabradine between January 2020 - May 2024. Demographic, clinical, and treatment-related variables were collected. Response variables were established according to indication, HF: heart rate (HR) and left ventricular ejection fraction (LVEF); SVT: HR.

Results

Thirteen patients (nine women) with a median age of 1.4 (1-4) months were included. Ivabradine was discontinued in five of the seven HF patients due to resolution of HF, control of HR, and improvement of LVEF. One patient discontinued ivabradine because of bradycardia. In the SVT group, four of the seven patients discontinued ivabradine after the resolution of tachyarrhythmia and improvement of HR. Two patients experienced bradycardia but did not require treatment discontinuation. HR reduction was statistically significant in both groups. In HF, the median initial ivabradine dose was 0.06 mg/kg/day and the maintenance dose was 0.2 mg/kg/day. In SVT, the initial and maintenance doses were 0.1 mg/kg/day and 0.24 mg/kg/day, respectively.

Conclusion

Ivabradine demonstrated favorable efficacy and safety results in patients under 6 months of age with HF or SVT.
Brigatinib can inhibit proliferation and induce apoptosis of human immortalized keratinocyte cells
Authors: Yang Qi , Zhao Dan , Ju Linjie , Cao Peng , Wei Jifu , Liu Zhixian
Published: February 2025

Background

Brigatinib is approved in multiple countries for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Despite its superior efficacy, the dermal toxicities caused by brigatinib cannot be overlooked. However, its underlying mechanism remains unknown.

Methods

The effects of brigatinib on the proliferation ability of human immortalized keratinocyte (HaCaT) cells were evaluated using Cell Counting Kit-8 (CCK-8) proliferation, colony formation, and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays. The effects of brigatinib on apoptosis were detected using Annexin FITC/PI and Acridine Orange (AO) staining assays. Cell cycle was assessed with flow cytometry. An analysis of transcriptome by RNA sequencing procedures (RNA-seq) was performed to reveal the key regulatory genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to find out the biological function and related signal pathways. The expressions of amphiregulin, epiregulin and transforming growth factor alpha (TGFA) and the protein levels of Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and Cleaved-Caspase three were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot assay.

Results

Brigatinib inhibits cell proliferation with an IC50 value of 2.9 μmol/L and significantly increases apoptosis rates. Transcriptome sequencing (RNA-seq) indicates that brigatinib could significantly downregulate the expression of amphiregulin, epiregulin and TGFA. In addition, we demonstrated that brigatinib reduced the protein expression of amphiregulin, epiregulin, TGFA, PI3K, AKT and phosphorylated AKT (p-AKT).

Conclusion

This study confirms the inhibition of HaCaT cells growth and progression by brigatinib and highlights the potential value of the PI3K/AKT pathway as a therapeutic target for brigatinib-induced dermal toxicities.
Potential activity of Ferula macrecolea essential oil for treating Giardia lamblia infection through modulating electrolytes and suppressing NF-κB p65 pathway
Authors: Salimikia Iraj , Yaghoubi Seyed Ehsan , Khalaf Amal Khudair , Masoori Leila , Ghasemian Yadegari Javad , Mahmoudvand Hossein
Published: February 2025

Background

The pharmacological treatment of Giardia lamblia infection involves the use of chemical agents, such as metronidazole (MNZ). However, these medications are associated with a range of adverse effects, and their effectiveness is not definitively established. In light of the previously discussed information and the recognized antimicrobial properties of Ferula macrecolea, this study aims to investigate both the in vitro and in vivo anti-giardial effects of F. macrecolea essential oil (FME) on G. lamblia infection.

Methods

Gas chromatography-mass spectrometry (GC-MS) was utilized to analyze the chemical composition of the prepared FME. The MTT colorimetric assay was employed to assess FME’s in vitro anti-giardial and cytotoxic activities. FME’s in vivo effects were evaluated compared to MNZ in mice infected with G. lamblia. Additionally, the effects of FME therapy on serum electrolyte levels and the expression levels of inflammatory cytokines were assessed.

Results

The primary components of FME were identified as terpinolene (78.72%), n-nonanal (4.47%), and linalool (4.35%). FME significantly reduced the viability and growth rate of G. lamblia trophozoites (IC50 = 21.6 μg/mL) and cysts (IC50 = 27.6 μg/mL) in a dose-dependent manner compared to the control group (p < 0.001). The CC50 value for FME against normal intestinal cells was determined to be 207.4 μg/mL. In vivo, assays demonstrated that the administration of various doses of FME, particularly in combination with MNZ over 7 days, resulted in a statistically significant reduction in the mean number and viability of Giardia cysts, serum level electrolytes (sodium and potassium), and the expression levels of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), nuclear factor κB p65 (NF-κB p65), and Toll-like receptor 4 (TLR-4) in mice with giardiasis (p < 0.001).

Conclusion

This study’s results demonstrate the extract’s efficacy in vitro against G. lamblia, exhibiting minimal cytotoxicity towards normal cells. Furthermore, the extract was shown to manage giardiasis in murine models by modulating electrolyte levels and inflammatory responses via suppressing the NF-κB p65/TLR pathways. However, further research is necessary to clarify the specific efficacy and mechanisms of action of the extract in combating G. lamblia infection.
Potential mechanism of traditional Chinese medicine intervention in gastric cancer: targeted regulation of autophagy
Authors: Sun Siyuan , Yu Wenqian , Zhang Guangheng , Li Xiangyu , Song Linjing , Lv Yehan , Chen Yi
Published: February 2025

Gastric cancer (GC) is a prevalent malignant tumor that originates from the epithelial cells of the gastric mucosa, predominantly in the form of adenocarcinoma. Extensive research has confirmed the significant role of autophagy in the initiation, progression, and chemoresistance of GC. The potential of traditional Chinese medicine (TCM) to exert anti-tumor effects by modulating autophagy has been demonstrated, particularly in the context of GC prevention and treatment. Natural products (NPs) have great therapeutic potential in the prevention and treatment of GC by targeting autophagy-related genes and signaling pathways to intervene in the biological behaviors of gastric cancer cells such as proliferation, metastasis, invasion and death. This article describes the molecular mechanisms and key markers of tumor autophagy, the signaling pathways involved in GC-associated autophagy (PI3K/AKT/mTOR, AMPK, MAPK, p53), and summarizes the mechanism of autophagy and Helicobacter pylori infection in GC, how autophagy interacts with apoptotic and iron-death processes and the wide-ranging influences that these factors play in the process. Finally, this paper systematically summarizes the natural compounds of terpenoids, polyphenols, alkaloids, saponins, and polysaccharides that modulate autophagy-related signaling pathways and potential targets for the treatment of GC, and evaluates the toxic effects of NPs, providing a more compelling rationale and direction for GC therapy.
Caveolin and oxidative stress in cardiac pathology
Authors: Zadorozny Lauren , Du Jiayue , Supanekar Neil , Annamalai Karthik , Yu Qing , Wang Meijing
Published: February 2025

Caveolins interact with signaling molecules within caveolae and subcellular membranes. Dysregulation of caveolin function and protein abundance contributes to cardiac pathophysiological processes, driving the development and progression of heart disease. Reactive oxygen species (ROS) play a critical role in maintaining cellular homeostasis and are key contributors to the pathophysiological mechanisms of cardiovascular disorders. Caveolins have been shown to modulate oxidative stress and regulate redox homeostasis. However, the specific roles of caveolins, particularly caveolin-1 and caveolin-3, in regulating ROS production during cardiac pathology remain unclear. This mini-review article highlights the correlation between caveolins and oxidative stress in maintaining cardiovascular health and modulating cardiac diseases, specifically in myocardial ischemia, heart failure, diabetes-induced metabolic cardiomyopathy, and septic cardiomyopathy. A deeper understanding of caveolin-mediated mechanisms may pave the way for innovative therapeutic approaches to treat cardiovascular diseases.
Dynamic changes in the transcriptome of tropical region-originated king grasses in response to cold stress
Authors: Lai Xianjun , Yan Junfeng , Chen Zihan , Zhang Yizheng , Luo Fan , Cai Guangze , Yan Lang
Published: February 2025

Introduction

Cold acclimatization in tropical region-originated plants involves complex gene expression reprogramming to adapt to fluctuating temperatures. However, the molecular mechanisms and gene networks regulating cold tolerance in king grass remain largely unknown.

Methods

To address this, we established a full-length reference transcriptome of king grass to enhance assembly quality and performed multiple time-point transcriptomic analyses following cold treatment at 4°C. Differentially expressed genes (DEGs) and transcription factors (TFs) involved in cold stress response were identified and analyzed through clustering and co-expression network analysis.

Results

A total of 13,056 DEGs were identified and classified into nine clusters via k-means analysis. The cold response exhibited three distinct phases: early (before 3 h), middle (6–24 h), and late (48–72 h). Early-responsive genes were enriched in glycolipid metabolism and photosynthesis, middle-stage genes in carbohydrate metabolism, and late-stage genes in cold stress, osmotic stress, and endogenous stimuli responses. Key regulators of the ICE-CBF-COR signaling module, including 13 positive and negative regulators, were identified. The co-expression network further revealed mutual regulatory interactions within this module, highlighting its role in cold stress adaptation.

Discussion

Our findings provide insights into the cold tolerance mechanisms of king grass, offering a genetic basis for modifying cold stress regulators. This research contributes to the broader understanding of low-temperature adaptive mechanisms in tropical plants and supports future breeding strategies for improved cold tolerance.
Ensiling characteristics, in vitro digestibility and bacterial community structure of mulberry leaf silage with or without the addition of cellulase, protease, and starch
Authors: Zhao Guoqiang , Wu Hao , Li Yangyuan , Huang Zhiyi , He Jiajun , Xie Xiangxue
Published: February 2025

Objective

This study aimed to investigate the effects of cellulase, protease, and starch on the fermentation quality, in vitro digestibility, and microbial community of mulberry leaf silage after 30d of ensiling.

Methods

Mulberry leaves (376 g/kg dry matter (DM)) were ensiled with four experimental treatments: i) CON, no additives; ii) CEL, added cellulase (120 U/g fresh matter [FM]); iii) CPR, added cellulase (120 U/g FM) and protease (50 U/g FM); and iv) CPS, added cellulase (120 U/g FM), protease (50 U/g FM), and starch (2% FM).

Results

All treatments with additives improved fermentation quality, showing higher DM (353 ~ 378 vs. 341 g/kg DM), lactic acid (LA) content (51.6 ~ 64.6 vs. 40.2 g/kg DM), lactic acid bacteria (LAB) counts (7.63 ~ 7.73 vs. 7.49 log10 CFU /g of FM), along with lower pH values (4.29 ~ 4.60 vs. 5.09), and DM losses (124 ~ 130 vs. 134 g/kg DM) compared to the CON group. All the additive treated groups showed higher in vitro digestibility of DM (698 ~ 720 vs. 618 g/kg DM), in vitro digestibility of NDF (395 ~ 412 vs. 336 g/kg DM), and ADF (277 ~ 298 vs. 232 g/kg DM) than CON. Among all the groups, the CPS group exhibited the highest DM content (378 g/kg DM), LA content (64.6 g/kg DM) and LAB counts (7.73 log10 CFU /g of FM), with the lowest pH value (4.29) and DM losses (124 g/kg DM). Additionally, the additive treatments increased abundance of bacteria like Firmicutes and Enteroccocus, while reducing Proteobacteria abundance, and resulted in lower diversity and richness of the microbial community. Specifically, CPR and CPS silages showed increased Pediococcus and decreased Enterobacter compared to CON and CEL, and CPS silage had a relatively high abundance of favorable Bacteroidota. Furthermore, the CPS silage exhibited upregulated genetic functions, energy and lipid metabolism, as well as metabolism of cofactors and vitamins compared to the other groups.

Conclusion

The combined application of cellulase, protease, and starch effectively improved the fermentation quality, in vitro digestibility, and microbial community of mulberry leaf silage over the 30-day ensiling period.
Transcriptomic and proteomic analysis of oil body associated protein dynamics in the biofuel feedstock Pennycress (Thlaspi arvense)
Authors: Luján María Ángeles , Claver Ana , Lorente Patricia , López M. Victoria , Alfonso Miguel
Published: February 2025

Pennycress (Thlaspi arvense) is an emerging feedstock for biofuel production because of its high seed oil content enriched in erucic acid. A combination of transcriptomic and proteomic tools was used to characterize the dynamics and relative abundance of the major oil body related proteins in the Pennycress seed. Our analysis identified 21 oleosins (OLE), 6 oil body associated proteins (OBAPs), 3 SEIPINS, 3 caleosins, 3 stereolisins and 3 lipid droplet associated proteins (LDAPs) in the Pennycress genome, showing high homology with respect to Arabidopsis or rapeseed. RNA-Seq analysis on five Pennycress seed maturation stages showed that most OLE and OBAP genes increased their expression with seed maturation, coinciding with the highest accumulation of triacylglycerol. Western-blot analysis of the OLE2 protein during seed maturation confirmed this result. However, OLE5 and SEIPIN1 genes showed higher expression at the early stages of seed maturation, suggesting that both proteins could be particularly involved in the initial stages of oil body formation. Proteomic analysis on oil body enriched fractions from the YELLOW and MATURE late seed maturation stages showed that all oleosin proteins were highly abundant in oil bodies. Caleosins and stereolisins were also highly abundant. Our results indicate the existence of differential expression patterns of oil body related genes during Pennycress seed maturation, suggesting different roles of these proteins for the formation and stabilization of oil bodies in the Pennycress seed.
TAL-SRX: an intelligent typing evaluation method for KASP primers based on multi-model fusion
Authors: Chen Xiaojing , Fan Jingchao , Yan Shen , Huang Longyu , Zhou Guomin , Zhang Jianhua
Published: February 2025

Intelligent and accurate evaluation of KASP primer typing effect is crucial for large-scale screening of excellent markers in molecular marker-assisted breeding. However, the efficiency of both manual discrimination methods and existing algorithms is limited and cannot match the development speed of molecular markers. To address the above problems, we proposed a typing evaluation method for KASP primers by integrating deep learning and traditional machine learning algorithms, called TAL-SRX. First, three algorithms are used to optimize the performance of each model in the Stacking framework respectively, and five-fold cross-validation is used to enhance stability. Then, a hybrid neural network is constructed by combining ANN and LSTM to capture nonlinear relationships and extract complex features, while the Transformer algorithm is introduced to capture global dependencies in high-dimensional feature space. Finally, the two machine learning algorithms are fused through a soft voting integration strategy to output the KASP marker typing effect scores. In this paper, the performance of the model was tested using the KASP test results of 3399 groups of cotton variety resource materials, with an accuracy of 92.83% and an AUC value of 0.9905, indicating that the method has high accuracy, consistency and stability, and the overall performance is better than that of a single model. The performance of the TAL-SRX method is the best when compared with the different integrated combinations of methods. In summary, the TAL-SRX model has good evaluation performance and is very suitable for providing technical support for molecular marker-assisted breeding and other work.
Mental imagery and stress: the mediating role of self-efficacy in competitive martial arts athletes
Authors: Di Corrado Donatella , Tortella Patrizia , Coco Marinella , Guarnera Maria , Tusak Matej , Parisi Maria Chiara
Published: February 2025

Introduction

Martial arts are diverse systems of combat practices, each with its unique techniques, philosophies, and histories. Mental imagery is a multisensory experience that integrates various senses to create vivid mental representations, evoking the physical attributes of people, places, or objects not currently within our perception. In sports contexts, studies have indicated that martial arts often use imagery to enhance performance.

Methods

This study aimed to investigate the mediating role of self-efficacy in the relationship between static (visualizing still scenes or concepts) and dynamic (focusing on motion and action) vividness, controllability (manipulating the imagery experience), and the degree of stress, in a group of 110 martial arts athletes (61 males and 49 females), aged between 21 and 23 years old (M = 22.47, SD = 0.75). Participants were competitive athletes of karate, taekwondo and judo, having a minimum of 13 years of training skill in the sport. They completed the Vividness of Visual Imagery Questionnaire, the Vividness of Movement Imagery Questionnaire-2, the Mental Image Transformation Task, The General Self-Efficacy Scale, and Measuring Psychological Stress Test.

Results

A 2 × 3 (gender × sport type) between groups MANOVA showed significant differences in imagery dimensions by sport type. The results of the mediation analysis showed that self-efficacy plays a mediating role between imagery and stress.

Discussion

The study advanced exploration in the field of mental imagery training, providing additional evidence for its importance in improving performance and managing stress in athletes.
Association between psychological depression and physical health in Chinese empty-nesters during the COVID-19 pandemic
Authors: Wang Shiyi , Fan Xiaojing , Li Fang , Zhou Zhongliang
Published: February 2025

Objectives

With the aging of the population becoming increasingly serious, the phenomenon of empty-nesters is also becoming more and more serious. The psychological problems of the empty-nester elderly are becoming more and more prominent, which may affect their physical health. This study aimed to quantify the association between psychological depression and physical health in the background of the COVID-19 pandemic.

Methods

A total of 7,835 empty-nesters over 60 years old were selected from the China Health and Retirement Longitudinal Study in 2020. Depressive symptoms were applied to measure psychological health. The outcome variables of physical health were measured by self-rated health (SRH), chronic disease, and limited basic activities of daily living (BADLs). Binary logistic regression models with odds ratios and 95% confidence intervals (CI) were applied to explore the association between psychological and physical health.

Results

Empty-nesters with depressive symptoms were 72% less likely to rate their health as good than empty-nesters without depressive symptoms (95%CI: 0.242–0.328). The rates of chronic disease for empty-nesters with depressive symptoms were 1.45 (95%CI: 1.300–1.622) times higher than those without depressive symptoms, and those with depressive symptoms were more likely to have limited BADLs than elderly without depressive symptoms (OR = 3.125, 95%CI: 2.757–3.543).

Conclusion

We found that among empty-nesters in China, depressive symptoms were negatively associated with good self-rated health and positively associated with chronic diseases and limitations in BADLs.
Tourette syndrome and brain stimulation therapy: a systematic review and meta-analysis of current evidence
Authors: Aloufi Alwaleed K. , Zahhar Jalal A. , Bader Mahmoud W. , Almutairi Maher B. , Alaaldeen Abdulqader , Hetta Omar E. , Gammash Abdulaziz M. , Almuntashiri Saleh , Binrabaa Ibrahim S. , Alsaleh Ahmad , AlSalem Moayyad
Published: February 2025

Background

Tourette syndrome (TS) is a neurological disorder characterized by tics, often associated with obsessive-compulsive disorder (OCD). Severe cases may require interventions such as deep brain stimulation (DBS) or repetitive transcranial magnetic stimulation (rTMS).

Methods

A thorough search was performed across PubMed/Medline, Embase, (CENTRAL), and Google Scholar. Studies comparing DBS and rTMS efficacy for TS were included if they reported YGTSS before and after treatment. Two independent reviewers screened the search results, extracted data, and assessed study quality using standardized tools.

Results

22 studies met the inclusion criteria, with a total of 222 participants. Analysis of RCTs investigating post-intervention rTMS vs baseline showed a statistically insignificant decrease in YGTSS (MD = -5.01, 95% CI: [-10.8, 0.79], P= 0.090) but a statistically significant decrease in YBOCS (MD = -6.6; 95% CI: [-11.64, -1.55], P= 0.010). However, post-intervention rTMS in RCT and non-randomized trials vs baseline showed a significant decrease in YGTSS (MD = -11.6; 95% CI: [-18.25, -4.94], P < 0.001) and YBOCS (MD = -7.5; 95% CI: [-11.85, -3.15], P < 0.001). Post-intervention DBS in RCT and non-RCTs vs baseline showed a significant decrease in YGTSS (MD = -18.29; 95% CI: [-24.93, -11.64], P < 0.001) and YBOCS (MD = -4.76; 95% CI: [-7.30, -2.21], P < 0.001). Analysis of RCTs investigating Post-intervention DBS vs baseline showed a significant decrease in YGTSS (MD = -14.71; 95% CI: [-19.78, -9.63], P <0.001) and YBOCS (MD = -5.04; 95% CI: [-8.28, -1.80], P = 0.002).

Conclusion

Our analysis revealed both DBS and rTMS improved TS and OCD symptoms, however the effect of rTMS on TS in RCTs was insignificant, suggesting DBS stimulation is more effective. Despite this, clinicians may still opt for rTMS before DBS due to its less invasive nature, the limited number of high-quality RCTs, and the lack of studies directly comparing rTMS and DBS.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023386856, identifier CRD42023386856.