bluuebunny/crossref_metadata_2025 huggingface dataset:
The Significance Of Ijtihad and Fatwa Methods in The Development Of Islamic Law In Indonesia
Authors: Agustono Ihwan
Published: January 2025

This article discusses the role of fatwas in the development of Islamic law, especially in Indonesia, which is institutionally represented by the Indonesian Ulema Council. The Qur'an and the Sunnah as the main sources of Islamic law are limited in terms of quantity, while the legal problems that arise in people's lives are increasingly complex and unlimited. To deal with various complex and novel problems, the legal requirements of which are sometimes not clearly stated in the Qur'an and the Sunnah, the application of ijtihad is absolutely necessary. One of the reasons for the formation of the Indonesian Ulema Council (MUI) was to face and respond to situations like this. As an Islamic institution that has the authority to issue fatwas, the MUI has an important position in the development of Islamic law in Indonesia. Therefore, the methods applied by the MUI in carrying out ijtihad and issuing fatwas related to various legal problems faced in society also have high urgency. This paper attempts to explore the ijtihad method used by the MUI in carrying out ijtihad and issuing fatwas. By using a qualitative approach, this research found that the MUI ijtihad method uses three approaches: the Nash Qath'i approach, the Qawli approach, and the Manhaji approach, which are based on the context.
Teaching healthy eating habits to children, to maintain good health throughout life through Greek primary school textbooks 1975-2020
Authors:   Université Montpellier III Paul Valery, Etudes Néo-helléniques, France, VASILOPOULOU Archontia
Published: January 2025

Introduction. The construction of nutritional consciousness is a continuous procedure, which starts from childhood. It has been found that eating habits are configured early in life. Objectives. To research the number of references and to evaluate their quality concerning the dietary habits theme in primary school textbooks, published since 1975. Additionally, the diachronic nature of this study allowed for comparison among the references encountered in the three different chronological periods. Material and methods. The books of primary school, including physical sciences subjects, constituted the body of the study, edited from 1975-2020, since they are the main source of nutritional information for students. Results. The methodology of study was defined as thematically analysis of the books content and was based on the categorization of words and phrases, according to their content. All the relevant refe-rences were searched and placed together in a table. The study of school books revealed four themes concerning the recommended food habits, such as the avoidance of overeating, the consumption of all the food groups, and daily meals and the preference of fresh fruit and vegetables. Conclusion. The content of the present books requires additions and improvements, in order to be in accordance with the updated scientist data and the contemporary mode of alimentation. [Introduction. L’enseignement des habitudes alimentaires saines est une procédure continue et complexe, qui est initiée depuis l’enfance. Objectifs. Rechercher le nombre de références et évaluer leur qualité concernant le thème des habitudes alimentaires dans les livres scolaires de primaire, édités depuis 1975. De plus, le caractère diachronique de cette étude permet la comparaison parmi les références retrouvées sur les trois différentes périodes chronologiques. Matériel et méthodes. Le corpus de la présente étude inclut les manuels scolaires grecs de primaire, qui ont été édités depuis 1975 jusqu’à 2020. Les livres choisis traitent des thèmes des sciences physiques.La méthodologie effectuée concerne l’analyse thématique de contenu des livres, qui est fondée sur le regroupement des mots et phrases selon leur contenu. Ainsi, toutes les références pertinentes dans les livres ont été relevées et regroupées au sein d’un tableau. Résultats. L’étude thématique des manuels examinés a relevé quatre sous-thèmes sur le thème des habitudes alimentaires saines. Ces sous-thèmes concer-nent des recommandations sur l’évitement de la surconsommation alimentaire, la consommation de tous les groupes d’aliments, la consommation de plusieurs repas par jour et la consommation des fruits et végétaux frais. Conclusion. Le contenu des manuels scolaires contemporains requiert des améliorations et des additions, conformément aux données scientifiques actualisées ainsi qu’au mode d’alimentation contemporain.]
Optimizing The Use of Production Factors of Rice Mina Farming
Authors: Rozanisa Isnaya , Wijayanti Irene Kartika Eka , Widjojoko Tatang , Solekan Muhamad
Published: January 2025

Mina padi farming is an innovative farming, namely the cultivation of fish and rice in paddy fields simultaneously. Limitations of farmers in obtaining factors of production require farmers to use factors of production efficiently. Therefore it is necessary to optimize to determine the optimal combination of production factors so that farmers get the maximum profit. This study aims to calculate the profits of mina padi farming, analyze the combination of the optimal use of production factors for mina padi farming, analyze the differences in the profits of mina padi farming in the first growing season with mina padi farming in the second growing season. Sampling using simple random sampling method. The analytical method uses profit analysis, optimization analysis, and different test. The profit of mina padi farming in the first planting season is Rp6,115,340.00 and in the second planting season is Rp6,487,589.00. The optimization model estimation result showed that the use of farming resource was not yet optimal. The use of production factors is not optimal as indicated by the excessive use of inputs such as capital, land, rice seeds, urea fertilizer, feed, and labor in the first growing season and the use of capital, land, ponska fertilizer, urea fertilizer, feed, and labor in the second growing season. There is a significant difference between the profits of mina padi farmers in the first growing season and the profits of mina padi farmers in the second growing season.
Analysis Of Farming Business And Income Contribution Of Cassava Farmers
Authors: Amalinda Harahap Fitri , Firdauzi Indrawan , Saputro Wahyu Adi
Published: January 2025

Cassava is an alternative food besides rice and corn. Farmers cultivate cassava as an additional alternative in their farming business. One of the locations that has good cassava production in Central Java is Banyumas Regency, precisely in Cilongok District. Many farmers in Cilongok cultivate cassava because it is easier to care for and there is already a market for it, especially for entrepreneurs in the surrounding area who buy farmers' harvests. This study aims to analyze the farming business and income contribution of cassava farmers in Banyumas. The method used in this study is quantitative descriptive. The selected sample was 30 cassava farmers in Cilongok District, Banyumas. The data analysis method is farming business analysis and calculation of income contribution. Based on the results of the study, it is known that the average cassava production in Cilongok District reaches 6,218 kilograms per hectare. Cassava farmers also have a cassava farming business income of Rp 2,831,150. The contribution of cassava income to farmers in Cilongok District reaches 20.77 percent.
Comparison of Labour Progression between Nulliparous Pregnant Women of Advanced Maternal Age and Young Nulliparous Women with Spontaneous Vaginal Delivery: A Retrospective Study in a Regional Core Hospital
Authors: Arakaki Ryosuke , Isono Wataru , Fukuda Hiroaki , Tanaka Junya , Minamino Arisa , Hayashi Shiko
Published: January 2025

Background: The number of nulliparous pregnant women of advanced maternal age, defined as 35 years or older, has increased in Japan, but there has not been a study comparing labour progression between pregnant women of advanced maternal age and young pregnant women. Therefore, we aimed to evaluate roughly whether labour progression times differed according to maternal age, with cervical dilation and foetal station used as the endpoints. Methods: We retrospectively reviewed the medical records of 1573 nulliparous women who had spontaneous vaginal delivery (929 patients), were administered an intravenous uterotonic agent (372 patients) or underwent emergency caesarean section (272 patients) at Kinan Hospital. We collected data on the patient characteristics and reviewed vaginal examination data for comparisons of labour progression. The endpoints were cervical dilation of 10 cm (full dilation) and foetal station of 2 cm, as these metrics are sufficient for vacuum-assisted vaginal delivery (sufficient descent). Data on the elapsed time between the recorded time of each stage of labour and the endpoint were obtained from two groups, namely, pregnant women of advanced maternal age and young pregnant women, and compared. Results: The percentages of women of advanced maternal age were higher among those who underwent emergency caesarean section and intravenous uterotonic agent administration. When the characteristics of the pregnant women of advanced maternal age were compared to those of the young pregnant women among the 929 patients with spontaneous vaginal delivery, differences in “blood loss amount” and “vacuum delivery status” were detected. However, regarding labour progression, there was almost no difference in any of the stages when the elapsed times between each stage and full dilation or sufficient descent were compared. Conclusions: We did not detect a clear impact of maternal age on labour progression in the groups of nulliparous women who had spontaneous vaginal delivery after women who underwent emergency caesarean section or intravenous uterotonic agent administration were excluded; however, further studies with larger sample sizes of women of advanced maternal age may be needed.
Factors Associated with the Severity of Stress Urinary Incontinence in Elderly Women
Authors: Li Suting , Wang Zhi , Yang Lian , Liu Shaoying , Jing Lili , Hong Li
Published: January 2025

Background: Stress urinary incontinence (SUI) is prevalent and significantly impacts morbidity. While some risk factors for SUI have been identified, those specifically related to the severity of SUI have not been thoroughly investigated. Methods: This study recruited elderly female patients with SUI, aged over 60 years old, from Wuhan, Hubei, China, between October and November 2020. Data collection encompassed demographic information, clinical features (including obstetric history, chronic diseases, Urogenital Distress Inventory-6 (UDI-6), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores), as well as physical examinations (including assessments of pelvic floor muscle strength, pelvic organ prolapse quantification (POP-Q) system, and pelvic floor ultrasound imaging). Results: Univariate analysis revealed that a history of postpartum urinary incontinence and chronic constipation significantly influenced the severity of SUI symptoms in the elderly (p < 0.05). Additionally, age, the number of vaginal deliveries, and a history of chronic cough were correlated with the severity of SUI symptoms, with p-values of 0.05, 0.08, and 0.12, respectively. Factors such as pelvic floor muscle strength, vaginal wall prolapse, uterine prolapse, and the morphology of the largest urethral opening all significantly impacted the severity of SUI symptoms in this population (p < 0.05). Multivariate logistic regression analysis identified age, the number of vaginal deliveries, chronic constipation, anterior vaginal wall prolapse, a history of postpartum urinary incontinence, and the shape of the maximum urethral opening as independent factors influencing SUI severity in older women (p < 0.05). The results of the Hosmer-Lemeshow test indicate that the model fits well (p = 0.37). Conclusions: Age, the number of vaginal deliveries, anterior vaginal wall prolapse, a history of postpartum urinary incontinence, chronic constipation, and a funnel-shaped maximum urethral opening are associated with increased severity of SUI symptoms in elderly women. The severity of SUI escalates with advancing age and an increased number of vaginal deliveries.
The Efficacy of Implementing Labor Analgesia Education via the WeChat Public Platform—A Randomized Controlled Study
Authors: Ma Lijun , Cheng Yan , Liu Hailian , Yang Wenjing , Yang Chen
Published: January 2025

Background: Previous research has revealed that utilizing videos or images to educate primiparas about labor analgesia yields significantly superior results. WeChat supports various types of media, making it an ideal carrier for educational content. We have established a WeChat public account where educational content is presented through videos, images, and relevant scientific articles. We will investigate the effectiveness of WeChat public platform in primiparas analgesia education. Methods: Primiparas were randomly assigned to either the WeChat public account education group (W group) or traditional bedside education group (B group). The labor analgesia knowledge questionnaires, self-rating anxiety scales, and the time taken for positioning were compared between the two groups. Additionally, satisfaction with labor analgesia was evaluated post-delivery. Results: A total of 90 primiparas were completed the study. Compared to the B group, primiparas in the W group had higher scores on labor analgesia knowledge questionnaire (55 ± 11.1 vs. 65 ± 9.2, p = 0.001), lower anxiety scores (51.4 ± 5.4 vs. 48.9 ± 4.6, p = 0.02), shorter positioning time (27.5 ± 7.9 s vs. 20.1 ± 9.2 s, p = 0.001) than those in the B group. The satisfaction of anesthesiologists with body positioning and the satisfaction of primiparas with labor analgesia were similar between the two groups. Conclusions: The use of WeChat public platform for labor analgesia education can enhance primiparas understanding and cooperation during the procedure, decreasing maternal anxiety. It also benefits anesthesiologists by improving work efficiency. It has significant clinical value and promising prospects for promotion. Clinical Trial Registration: The study was registered with the Chinese Clinical Trial Registry (ChiCTR1900025231).
Update on the Progress of Musashi-2 in Malignant Tumors
Authors: Niu Yiting , Zhou Tao , Li Yanjun
Published: January 2025

Since the discovery of the Musashi (MSI) protein, its ability to affect the mitosis of Drosophila progenitor cells has garnered significant interest among scientists. In the following 20 years, it has lived up to expectations. A substantial body of evidence has demonstrated that it is closely related to the development, metastasis, migration, and drug resistance of malignant tumors. In recent years, research on the MSI protein has advanced, and many novel viewpoints and drug resistance attempts have been derived; for example, tumor protein p53 mutations and MSI-binding proteins lead to resistance to protein arginine N-methyltransferase 5-targeted therapy in lymphoma patients. Moreover, the high expression of MSI2 in pancreatic cancer might suppress its development and progression. As a significant member of the MSI family, MSI2 is closely associated with multiple malignant tumors, including hematological disorders, common abdominal tumors, and other tumor types (e.g., glioblastoma, breast cancer). MSI2 is highly expressed in the majority of tumors and is related to a poor disease prognosis. However, its specific expression levels and regulatory mechanisms may differ based on the tumor type. This review summarizes the research progress related to MSI2 in recent years, including its occurrence, migration mechanism, and drug resistance, as well as the prospect of developing tumor immunosuppressants and biomarkers.
Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder
Authors: Szabó Ágnes , Galla Zsolt , Spekker Eleonóra , Szűcs Mónika , Martos Diána , Takeda Keiko , Ozaki Kinuyo , Inoue Hiromi , Yamamoto Sayo , Toldi József , Ono Etsuro , Vécsei László , Tanaka Masaru
Published: January 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders. The majority of KYNA is produced by the aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little is known about the consequences of deleting the KYN enzyme gene. Methods: In CRISPR/Cas9-induced aadat knockout (kat2-/-) mice, we examined the effects on emotion, memory, motor function, Trp and its metabolite levels, enzyme activities in the plasma and urine of 8-week-old males compared to wild-type mice. Results: Transgenic mice showed more depressive-like behaviors in the forced swim test, but not in the tail suspension, anxiety, or memory tests. They also had fewer center field and corner entries, shorter walking distances, and fewer jumping counts in the open field test. Plasma metabolite levels are generally consistent with those of urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, and indole-3-acetic acid levels were lower; enzyme activities in KATs, kynureninase, and monoamine oxidase/aldehyde dehydrogenase were lower, but kynurenine 3-monooxygenase was higher; and oxidative stress and excitotoxicity indices were higher. Transgenic mice displayed depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits, coupled with a decrease in KYNA, a shift of Trp metabolism toward the KYN-3-hydroxykynurenine pathway, and a partial decrease in the gut microbial Trp-indole pathway metabolite. Conclusions: This is the first evidence that deleting the aadat gene induces depression-like behaviors uniquely linked to experiences of despair, which appear to be associated with excitatory neurotoxic and oxidative stresses. This may lead to the development of a double-hit preclinical model in despair-based depression, a better understanding of these complex conditions, and more effective therapeutic strategies by elucidating the relationship between Trp metabolism and PTSD pathogenesis.
Inhibition of p70 Ribosomal S6K1 Protects the Myocardium against Ischemia/Reperfusion-Induced Necrosis through Downregulation of RIP3
Authors: Shang Hui , Shi Jinjin , Zhu Jun , Guo Yunfeng , Wang Xiaoyan
Published: January 2025

Background: Myocardial ischemia-reperfusion (I/R) injury refers to cell damage that occurs as a consequence of the restoration of blood circulation following reperfusion therapy for cardiovascular diseases, and it is a primary cause of myocardial infarction. The search for nove therapeutic targets in the context of I/R injury is currently a highly active area of research. p70 ribosomal S6 kinase (S6K1) plays an important role in I/R induced necrosis, although the specific mechanisms remain unclear. Objective: This study aims to explore the effects of inhibiting S6K1 on myocardial I/R injury and its potential mechanisms. Methods: A rat myocardial I/R model was created and treated with the S6K1-specific inhibitor PF-4708671. Hematoxylin-eosin (H&E) staining was applied to evaluate the pathological changes in cardiac tissues. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to measure the area of myocardial infarction (MI). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of increase in left ventricular pressure (+dp/dtmax), and the maximum rate of the decrease in left ventricular pressure (-dp/dtmax) were measured using ultrasonic echocardiography. The expression levels of cardiac troponin-1 (cTn-1), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), and aspartate aminotransferase (AST) were determined by enzyme-linked immunosorbent assay (ELISA). Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and propidium iodide (PI) staining were used to examine the apoptosis and necrosis of myocardial tissues. The expressions of apoptotic-related proteins, and key molecules of necrosis were detected by western blot. The relationship between S6K1 and receptor-interacting protein kinase 3 (RIP3) was analyzed by immunoprecipitation. Results: Inhibition of S6K1 reduces I/R-induced myocardial tissue damage, improves myocardial function, and inhibits myocardial tissue necrosis (p < 0.05). In addition, RIP3 is a direct target of S6K1, and activation of RIP3 blocked the protective effect of the S6K1 inhibitor PF-4708671 against myocardial I/R injury (p < 0.05). Conclusion: Inhibition of S6K1 protects against myocardial I/R injury by down-regulating RIP3, suggesting that targeting S6K1 may offer a novel approach for intervention in myocardial I/R injury.
tiRNA-Gln-CTG is Involved in the Regulation of Trophoblast Cell Function in Pre-eclampsia and Serves as a Potent Biomarker
Authors: Wang Yixiao , Ji Xiaohong , Shi Hengmei , Liu Sicong , Yu Hong
Published: January 2025

Background: Pre-eclampsia (PE) is a gestational disorder that significantly endangers maternal and fetal health. Transfer ribonucleic acid (tRNA)-derived small RNAs (tsRNAs) are important in the progression and diagnosis of various diseases. However, their role in the development of PE is unclear. Consequently, we detected the expression profiles of tsRNAs in the plasma of patients with PE as well as those in the plasma of the healthy control group, and a multiplicity of experiments were conducted with the aim of clarifying their roles in the occurrence and development of PE and the feasibility of serving as predictive biomarkers for this disorder. Methods: High-throughput sequencing of tsRNA in plasma from PE cases was performed to evaluate its potential as a diagnostic or therapeutic biomarker. The function of tsRNA in trophoblasts was explored using the HTR-8/SVneo cell line. Plasma from pregnant women with suspected PE was analyzed to assess the potential of tsRNA to act as a predictive marker of PE. Results: High-throughput sequencing of tsRNA was performed on plasma from pregnant women with PE and from healthy pregnant controls. Analysis revealed a significant reduction in the level of tRNA-derived stress-inducing RNA (tiRNA)-Gln-CTG in the plasma (p < 0.001) and placenta (p < 0.001) of pregnant women with PE, suggesting its potential involvement in the development of this condition. tiRNA-Gln-CTG was identified in the cytoplasm and nucleus of HTR-8/SVneo cells. In vitro experiments revealed that tiRNA-Gln-CTG influences the proliferation, cycling, migration, and invasion of HTR-8/SVneo cells, possibly by targeting the 3′UTR region of thrombospondin-2 messenger ribonucleic acid (mRNA) for degradation. Extracellular vesicle (EV) carriers may mediate the level of tiRNA-Gln-CTG in the circulation. Y-box binding protein-1 (YBX1) may be involved in loading tiRNA-Gln-CTG into EVs. The sensitivity of low tiRNA-Gln-CTG levels for predicting the onset of PE in suspected cases was 91.7% within 1 week of delivery, 85.7% within 4 weeks of delivery, and 89.3% before delivery, with corresponding specificities of 84.5%, 79.2%, and 73.4%, respectively. Conclusions: tiRNA-Gln-CTG significantly influences trophoblast function and is associated with the development of PE. It can serve as an effective biomarker for predicting PE progression within one week of delivery in women with suspected PE.
Monocyte and Macrophage in Follicular Liquid: Predictive Markers of Embryo Quality in Women with Obesity and Infertility
Authors: Merkulov Evgeny D. , Prozorova Anastasia V. , Samoilova Iuliia G. , Svarovsky Dmitry A. , Sidorenkova Kira A. , Spirina Liudmila V. , Stakheeva Marina N. , Timofeeva Oxana S. , Petrov Ilya A.
Published: January 2025

Background: Over the past five years, the pregnancy rate in assisted reproductive technology (ART) programs in Russia has remained relatively stable. The aim of this study was to assess the distribution of monocyte and macrophage subsets in the blood and follicular fluid of infertile women undergoing assisted reproductive technology. Methods: The study involved 45 women with a mean age of 35 ± 4.66 years. Monocytes and macrophages were identified using flow cytometry. Results: We observed a decrease in the CD68+CD163+CD206+ and the CD68+CD163–CD206+ cells in patients with a body mass index (BMI) >25 by 0.19 times and 6.56 times, respectively, compared to the group with a BMI <25 (p = 0.031). Patients with fair oocyte quality had 3.6 times more oocytes than those with poor quality (p = 0.010). The relative content of CD14+163–206+ monocytes was found to be 24.15 times higher in the follicular fluid of women with poor embryo quality compared to the group with good embryos (p = 0.010). We also noted that the number of oocytes increased in women with male factor infertility (p = 0.020) and those with unspecified infertility when compared to tubal infertility. An increase in the relative content of CD14+163+206+ in the blood was higher in women with other causes of female infertility compared to those with male factor infertility (p = 0.010). The relative content of M2-monocytes (CD14+163+206–) in the blood was 4.38 times higher in women with male factor infertility than in women with unexplained infertility (p = 0.010). Conclusions: A critical component of the inflammatory reaction in patients undergoing in vitro fertilization (IVF) involves more than just the activation of pro-inflammatory cells in response to ovarian stimulation. Our research shows that changes in the distribution of monocytes and macrophages can influence embryo implantation success and pregnancy outcomes in women. These processes are influenced by various infertility-related factors, including those mentioned above. However, these findings are preliminary and require further investigation.
Atomized Neutrophil Membrane-coated MOF Nanoparticles for Direct Delivery of Dexamethasone for Severe Pneumonia
Authors: Yang Yixiao , Yan Lizhen , Zhang Han , Xiao Chuanguang , Wang Kai
Published: January 2025

Background: Dexamethasone has proven life-saving in severe acute respiratory syndrome (SARS) and COVID-19 cases. However, its systemic administration is accompanied by serious side effects. Inhalation delivery of dexamethasone (Dex) faces challenges such as low lung deposition, brief residence in the respiratory tract, and the pulmonary mucus barrier, limiting its clinical use. Neutrophil cell membrane-derived nanovesicles, with their ability to specifically target hyper-activated immune cells and excellent mucus permeability, emerge as a promising carrier for pulmonary inhalation therapy. Methods: We designed a novel UiO66 metal-organic framework nanoparticle loaded with Dex and coated with neutrophil cell membranes (UiO66-Dex@NMP) for targeted therapy of severe pneumonia. This was achieved by loading Dex into UiO66 pores and subsequently coating with neutrophil membranes for functionalization. Results: Drug release experiments revealed UiO66-Dex@NMP to exhibit favorable sustained-release properties. Additionally, UiO66-Dex@NMP demonstrated excellent targeting capabilities both in vitro and in vivo. In a mouse model of lipopolysaccharide (LPS)-induced pneumonia, UiO66-Dex@NMP significantly reduced lung inflammation compared to both the control model and Dex administered via inhalation. Histopathological analysis further confirmed UiO66-Dex@NMP’s ability to alleviate lung tissue damage. Conclusions: UiO66-Dex@NMP represents a novel and safe inhaled delivery carrier for Dex, offering valuable insights into the clinical management of respiratory diseases, including severe pneumonia.
Heterogeneity in Fluorescence-Stained Sperm Membrane Patterns and Their Dynamic Changes Towards Fertilization in Mice
Authors: Hirai Momoka , Kishigami Satoshi
Published: January 2025

Background: Sperm represent a heterogeneous population crucial for male reproductive success. Additionally, sperm undergo dynamic changes during maturation and capacitation. Despite these well-established processes, the complex nature of sperm heterogeneity and membrane dynamics remains elusive. The composition of phospholipids in the sperm membrane changes dynamically during maturation, with their release occurring during capacitation. This study aims to investigate the heterogeneity and dynamic changes in the sperm membrane during maturation and capacitation towards fertilization by visualizing these membrane dynamics. Methods: Sperm were collected from the cauda epididymis or testis of Institute of Cancer Research (ICR) male mice and stained with MemBright dye (commercial name: MemGlow™-560, MG-560), a fluorogenic live-cell membrane probe. Staining was performed either before, during, or after incubation for capacitation. In pre-staining experiments, sperm were stained with MG-560 before capacitation and then incubated to induce capacitation. Acrosome-reacted sperm were assessed after staining with peanut agglutinin FITC (PNA-Lectin FITC). Stained sperm were observed using fluorescence or confocal microscopy. Results: MG-560-stained sperm from the epididymis before capacitation showed four staining patterns: head-midpiece-tail (HMT), head-midpiece (HM), head (H), midpiece (M) positive, or totally negative, with ratios remaining unchanged during capacitation (30.5%, 29%, 11.3%, 3.7%, and 25.5%, respectively). In contrast, all testicular sperm were negative for staining. Pre-stained sperm exhibited an increased number of HM and M patterns over time, whereas the number of HMT-stained sperm decreased. Consistently, spontaneous acrosome-reacted sperm were detected predominantly in HM- or M-stained sperm. After in vitro fertilization (IVF) using pre-stained sperm, zona pellucida-attached sperm were mostly negative for staining. Finally, all sperm detected in the perivitelline space were only negative. Conclusions: Mature sperm membranes stained with MG-560 exhibited heterogeneous and dynamic changes during the capacitation and fertilization process. MG-560 staining identified sperm with the potential to undergo the acrosome reaction, and these MG-560-positive sperm eventually became negative as they penetrated the zona pellucida for fertilization. Thus, the MG-560 staining patterns likely reflect the physiological state and potential of the sperm. These findings provide new insights into sperm heterogeneity and dynamics, and this staining method may also prove useful for assessing sperm quality.
Telomere Length and Oxidative Damage in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis
Authors: Ma Leping , Liu Cui , Song Ran , Qian Yeping , Zhang Feng
Published: January 2025

Background: Autism spectrum disorder (ASD) has been reported to confer an increased risk of natural premature death. Telomere erosion caused by oxidative stress is a common consequence in age-related diseases. However, whether telomere length (TL) and oxidative indicators are significantly changed in ASD patients compared with controls remains controversial. The aim of this study was to determine the associations of ASD with TL and oxidative indicators by performing a meta-analysis of all published evidence. Methods: The PubMed and Embase databases were searched for articles published up to April, 2024. The effect size was expressed as standardized mean difference (SMD) and 95% confidence interval (CI) via Stata 15.0 software. Results: Thirty-nine studies were included. Pooled results showed that compared with controls, children and adolescents with ASD were associated with significantly shorter TL (SMD = –0.48; 95% CI = –0.66– –0.29; p < 0.001; particularly in males), lower total antioxidant capacity (TAC: SMD = –1.15; 95% CI = –2.01– –0.30; p = 0.008), and higher oxidative DNA (8-hydroxy-2′-deoxyguanosine, 8-OHdG: SMD = 0.63; 95% CI = 0.03–1.23; p = 0.039), lipid (hexanolyl-lysine, HEL: SMD = 0.37; 95% CI = 0.13–0.62; p = 0.003), and protein (3-nitrotyrosine, 3-NT: SMD = 0.86; 95% CI = 0.21–1.51; p = 0.01; dityrosine, DT: SMD = 0.66; 95% CI = 0.521–0.80; p < 0.01) damage. There were no significant differences between ASD and controls in 8-isoprostane and oxidative stress index after publication bias correction, and in N-formylkynurenine during overall meta-analysis. Conclusions: TL, 8-OHdG, TAC, HEL, 3-NT, and DT represent potential biomarkers for prediction of ASD in children and adolescents.
Effects of Electrical Stimulation on Activation of Mirror Neuron Network in Healthy Adults during Motor Execution and Imitation: An fNIRS Study
Authors: Cui Yao , Cong Fang , Huang Fu-Biao , Zeng Ming , Wang Jun
Published: January 2025

Background: Observation, execution, and imitation of target actions based on mirror neuron network (MNN) have become common physiotherapy strategies. Electrical stimulation (ES) is a common intervention to improve muscle strength and motor control in rehabilitation treatments. It is possible to enhance MNN’s activation by combining motor execution (ME) and motor imitation (MI) with ES simultaneously. This study aims to reveal whether ES could impact cortical activation during ME and MI. Methods: We recruited healthy individuals and assigned them randomly to the control group (CG) or experiment group (EG). Participants in EG performed ME and MI tasks with ES, while participants in CG performed the same two tasks with sham ES. We utilized functional near-infrared spectroscopy (fNIRS) to detect brain activation of MNN during ME and MI with and without ES, a randomized block design experiment paradigm was designed. Descriptive analysis of oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) were used to show the hemoglobin (Hb) concentration changes after different event onsets in both CG and EG, a linear mixed-effects model (LMM) of HbO data was employed to analyze the effect of ES on the activation of MNN. Results: A total of 102 healthy adults were recruited and 72 participants’ data were analysed in the final report. The block averaged Hb data showed that HbO concentration increased and HbR concentration decreased in most MNN regions during ME and MI in both groups. The LMM results showed that ES can significantly improve the activation of inferior frontal gyrus, middle frontal gyrus, and precentral gyrus during MI, the supplementary motor area, inferior parietal lobule, and superior temporal gyri showed increased activation, but without statistical significance. Although the results did not reach statistical significance during ME, ES still showed positive effects on increased overall activations. Conclusions: In this study, we present potential novel rehabilitation approaches that combines MNN strategies and low-frequency ES to enhance cortical activation. Our results revealed that ES has potential to increase activation of most MNN brain areas, providing evidence for related rehabilitative interventions and device development. Clinical Trial Registration: This study was registered on the China Clinical Trial Registration Center (identifier: ChiCTR2200064082, registered 26, September 2022, https://www.chictr.org.cn/showproj.html?proj=178285).
The Robustness of White Matter Brain Networks Decreases with Aging
Authors: Huang Chenye , Wang Xie , Xie Daojun
Published: January 2025

Background: White matter (WM) is a principal component of the human brain, forming the structural basis for neural transmission between cortico-cortical and subcortical structures. The impairment of WM integrity is closely associated with the aging process, manifesting as the reorganization of brain networks based on graph theoretical analysis of complex networks and increased volume of white matter hyperintensities (WMHs) in imaging studies. Methods: This study investigated changes in the robustness of WM brain networks during aging and assessed their correlation with WMHs. We constructed WM brain networks for 159 volunteers from a community sample dataset using diffusion tensor imaging (DTI). We then calculated the robustness of these networks by simulating neurodegeneration based on network attack analysis, and studied the correlations between WM network robustness, age, and the proportion of WMHs. Results: The analysis revealed a moderate, negative correlation between WM network robustness and age, and a weak and negative correlation between WM network robustness and the proportion of WMHs. Conclusions: These findings suggest that WM pathologies are associated with aging and offer new insights into the imaging characteristics of the aging brain.
Changes in the Parietal Lobe Subregion Volume at Various Stages of Alzheimer’s Disease and the Role in Cognitively Normal and Mild Cognitive Impairment Conversion
Authors: Lu Fang , Ma Qing , Shi Cailing , Yue Wenjun
Published: January 2025

Background: Volume alterations in the parietal subregion have received less attention in Alzheimer’s disease (AD), and their role in predicting conversion of mild cognitive impairment (MCI) to AD and cognitively normal (CN) to MCI remains unclear. In this study, we aimed to assess the volumetric variation of the parietal subregion at different cognitive stages in AD and to determine the role of parietal subregions in CN and MCI conversion. Methods: We included 662 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, including 228 CN, 221 early MCI (EMCI), 112 late MCI (LMCI), and 101 AD participants. We measured the volume of the parietal subregion based on the Human Brainnetome Atlas (BNA-246) using voxel-based morphometry among individuals at various stages of AD and the progressive and stable individuals in CN and MCI. We then calculated the area under the curve (AUC) of the receiver operating characteristic (ROC) curve to test the ability of parietal subregions to discriminate between different cognitive groups. The Cox proportional hazard model was constructed to determine which specific parietal subregions, alone or in combination, could be used to predict progression from MCI to AD and CN to MCI. Finally, we examined the relationship between the cognitive scores and parietal subregion volume in the diagnostic groups. Results: The left inferior parietal lobule (IPL)_6_5 (rostroventral area 39) showed the best ability to discriminate between patients with AD and those with CN (AUC = 0.688). The model consisting of the left IPL_6_4 (caudal area 40) and bilateral IPL_6_5 showed the best combination for predicting the CN progression to MCI. The left IPL_6_1 (caudal area 39) showed the best predictive power in predicting the progression of MCI to AD. Certain subregions of the volume correlated with cognitive scales. Conclusion: Subregions of the angular gyrus are essential in the early onset and subsequent development of AD, and early detection of the volume of these regions may be useful in identifying the tendency to develop the disease and its treatment.
The Impact of Optical Undersampling on the Ca2+ Signal Resolution in Ca2+ Imaging of Spontaneous Neuronal Activity
Authors: Milicevic Katarina D. , Ivanova Violetta O. , Brazil Tina N. , Varillas Cesar A. , Zhu Yan M.D. , Andjus Pavle R. , Antic Srdjan D.
Published: January 2025

Background: In neuroscience, Ca2+ imaging is a prevalent technique used to infer neuronal electrical activity, often relying on optical signals recorded at low sampling rates (3 to 30 Hz) across multiple neurons simultaneously. This study investigated whether increasing the sampling rate preserves critical information that may be missed at slower acquisition speeds. Methods: Primary neuronal cultures were prepared from the cortex of newborn pups. Neurons were loaded with Oregon Green BAPTA-1 AM (OGB1-AM) fluorescent indicator. Spontaneous neuronal activity was recorded at low (14 Hz) and high (500 Hz) sampling rates, and the same neurons (n = 269) were analyzed under both conditions. We compared optical signal amplitude, duration, and frequency. Results: Although recurring Ca2+ transients appeared visually similar at 14 Hz and 500 Hz, quantitative analysis revealed significantly faster rise times and shorter durations (half-widths) at the higher sampling rate. Small-amplitude Ca2+ transients, undetectable at 14 Hz, became evident at 500 Hz, particularly in the neuropil (putative dendrites and axons), but not in nearby cell bodies. Large Ca2+ transients exhibited greater amplitudes and faster temporal dynamics in dendrites compared with somas, potentially due to the higher surface-to-volume ratio of dendrites. In neurons bulk-loaded with OGB1-AM, cell nucleus-mediated signal distortions were observed in every neuron examined (n = 57). Specifically, two regions of interest (ROIs) on different segments of the same cell body displayed significantly different signal amplitudes and durations due to dye accumulation in the nucleus. Conclusions: Our findings reveal that Ca2+ signal undersampling leads to three types of information loss: (1) distortion of rise times and durations for large-amplitude transients, (2) failure to detect small-amplitude transients in cell bodies, and (3) omission of small-amplitude transients in the neuropil.
Dynamics of HDL-Cholesterol Following a Post-Myocardial Infarction Cardiac Rehabilitation Program
Authors: Bertolín-Boronat Carlos , Merenciano-González Héctor , Marcos-Garcés Víctor , Martínez-Mas María Luz , Climent Alberola Josefa Inés , Pérez Nerea , López-Bueno Laura , Esteban-Argente María Concepción , Valls Reig María , Arizón Benito Ana , Payá Rubio Alfonso , Ríos-Navarro César , de Dios Elena , Gavara Jose , Sanchis Juan , Bodi Vicente
Published: January 2025

Background: Exercise-based cardiac rehabilitation programs (CRP) are recommended for patients following acute coronary syndrome to potentially improve high-density lipoprotein cholesterol (HDL-C) levels and prognosis. However, not all patients reach target HDL-C levels. Here we analyze the dynamics and predictors of HDL-C increase during CRP in patients following ST-segment elevation myocardial infarction or occlusion myocardial infarction. Methods: We conducted a prospective study of myocardial infarction patients who completed exercise-based Phase 2 CRP. Data was collected on clinical variables, cardiovascular risk factors, treatment goals, pharmacological therapy, and health outcomes through questionnaires at the beginning and at the end of Phase 2 CRP. Lipid profile analysis was performed before discharge, 4 to 6 weeks after discharge, and at the end of Phase 2 CRP. Changes in lipid profiles were evaluated, and predictors of failure to increase HDL-C levels were identified by binary logistic regression analysis. Results: Our cohort comprised 121 patients (mean age 61.67 ± 10.97 years, 86.8% male, and 47.9% smokers before admission). A significant decrease in total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) were noted, along with an increase in HDL-C (43.87 ± 9.18 vs. 39.8 ± 10.03 mg/dL, p < 0.001). Patients achieving normal HDL-C levels (>40 mg/dL in men and >50 mg/dL in women) significantly increased from 34.7% at admission to 52.9% the end of Phase 2. Multivariable analysis revealed smoking history (hazard ratio [HR] = 0.35, 95% confidence interval [CI], 0.11–0.96, p = 0.04), increased reduction in total cholesterol (HR = 0.94, 95% CI, 0.89–0.98, p = 0.004), and increased reduction in LDL-C (HR = 0.94, 95% CI, 0.89–0.99, p = 0.01) were inversely associated with failure to increase HDL-C levels. Conversely, higher HDL-C before CRP (HR = 1.15, 95% CI, 1.07–1.23, p < 0.001) and increased lipoprotein (a) (HR = 1.01, 95% CI, 1–1.02, p = 0.04) predicted failure to increase HDL-C levels. No significant correlations were found with Mediterranean diet adherence, weekly physical activity, training modalities, or physical fitness parameters. Conclusions: Participation in an exercise-based Phase 2 CRP led to mild but significant increases in HDL-C. Smoking history and patients experiencing substantial reductions in total cholesterol and LDL-C were more likely to experience HDL-C increases, unlike those with higher HDL-C and lipoprotein (a) levels before CRP.
Cardiopulmonary Exercise Testing: Deciphering Cardiovascular Complications in Systemic Sclerosis
Authors: Giubertoni Ailia , Bellan Mattia , Cumitini Luca , Patti Giuseppe
Published: January 2025

Cardiac manifestations in systemic sclerosis (SSc) are variable and are associated with a poor prognosis, frequently resulting in impaired right ventricular function and heart failure. A high proportion of patients with SSc experience pulmonary arterial hypertension (PAH), interstitial lung disease, or myocardial involvement, all of which can lead to exercise intolerance. In this context, cardiopulmonary exercise testing (CPET) is a useful tool for diagnosing exercise intolerance, elucidating its pathophysiology, and assessing its prognosis. CPET can also identify patients with SSc at higher risk of developing PAH. Despite its utility, current guidelines for CPET do not include the evaluation of patients with SSc, nor do standard SSc management guidelines consider CPET in the clinical work-up. This review summarizes the development, supporting evidence, and application of CPET in assessing cardiac involvement in patients with SSc.
Prognostic Value of the Tricuspid Regurgitation Impact on Outcomes (TRIO) Score in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Wang Jizhong , Chen Yuanwei , Zhang Xuxing , Luo Songyuan , Li Jie , Pei Fang , Luo Jianfang
Published: January 2025

Background: Prognosis assessments for transcatheter aortic valve implantation (TAVI) patients remain challenging, particularly as the indications for TAVI expand to lower-risk patients. This study assessed the prognostic value of the tricuspid regurgitation impact on outcomes (TRIO) score in patients after TAVI. Methods: This single-center study included 530 consecutive patients who underwent TAVI. Patients with a TRIO score >4 were compared to those with a score ≤4. The primary outcome was all-cause mortality, while secondary outcomes included complications defined by the Valve Academic Research Consortium 2 (VARC-2) criteria and major adverse cardiovascular events (MACEs), including mortality, stroke, and heart failure rehospitalization. Results: Over a mean follow-up period of 22 months, patients with a TRIO score >4 had significantly higher rates of mortality (11.5% vs. 3.1%, p < 0.001) and MACEs (14.9% vs. 3.6%, p < 0.001). Multivariable Cox regression analysis identified a TRIO score >4 as an independent risk factor for all-cause mortality (hazard ratio (HR): 2.41, 95% confidence interval (CI): 1.08–5.37, p = 0.032) and MACEs (HR: 2.78, 95% CI: 1.34–5.75, p = 0.006). Patients with a higher TRIO score also had significantly higher rates of stroke (3.1% vs. 0.5%, p = 0.028), acute kidney injury (10.1% vs. 4.3%, p = 0.011), and MACEs (14.9% vs. 3.6%, p < 0.001) within 30 days after TAVI. Conclusions: The TRIO score was associated with all-cause mortality and MACEs in patients after a TAVI. The TRIO score could serve as a convenient tool for risk stratification in clinical practice, aiding in identifying high-risk patients.