bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Risk Factors for Bleeding and Recurrence of Ovarian Endometriomas after Laparoscopic Surgery and Its Impact on Pregnancy Outcomes
Authors: Han Juanjuan , Zheng Lin
Published: January 2024

Background: Ovarian endometriomas are a common gynecological disease in women of childbearing age. Laparoscopic surgery is the gold standard surgical procedure for treating patients with ovarian endometriomas. However, laparoscopic postoperative bleeding, recurrence, and pregnancy failure are still unavoidable problems for many patients. Methods: A retrospective analysis was performed of 212 patients with ovarian endometriomas treated by laparoscopic surgery in our hospital from January 2016 to December 2020, with postoperative follow-up for 2 years. The researchers completed the follow-up by telephone, email, and outpatient review. Chi-square test was used to analyze the relationship between their clinical characteristics and postoperative bleeding, recurrence, and pregnancy along with logistic regression analysis of the risk factors for postoperative bleeding and recovery. Also, the use of logistic regression analysis may influence the factors influencing pregnancy outcome after laparoscopy. Results: The postoperative pregnancy success rate in 212 patients with ovarian endometriomas was 63.7%. The incidence of bleeding after surgery was 31.6% and the recurrence rate was 21.2%. The results of the logistic-regression analysis demonstrated that, age (odds ratio (OR) = 1.208, p = 0.001), combined with deep infiltrating endometriosis (DIE) (OR = 5.18, p = 0.023), cystic diameter ≥5 cm (OR = 0.076, p = 0.005), bleeding during the operation ≥50 mL (OR = 25.769, p = 0.000) and intraoperative bleeding (OR = 1.295, p = 0.000) were independent risk factors for postoperative bleeding. Severe dysmenorrhea (OR = 6.189, p = 0.004), cystic diameter ≥5 cm (OR = 8.502, p = 0.001), bilaterality (OR = 85.214, p = 0.001) and intraoperative bleeding (OR = 0.911, p = 0.003) were independent risk factors for the recurrence of ovarian endometriomas. By logistic regression analysis, age, bilaterality, the revised American Fertility Society (r-AFS) stage ≥Ⅲ were all related factors for postoperative pregnancy (p < 0.05). Conclusions: Age, combined with deep infiltrating endometriosis, cystic diameter, bleeding during the operation and intraoperative bleeding were all independent risk factors for postoperative bleeding. Severe dysmenorrhea, bilaterality, cystic diameter and intraoperative bleeding were independent risk factors for the recurrence of ovarian endometriomas. Age, bilaterality, r-AFS stage ≥Ⅲ were related factors for postoperative pregnancy.
The Relationship between Maternal Perinatal Depression and Offspring Depression: A Meta-Analysis
Authors: Yang Qing , Mi Wei , Su Fang , Song Wei
Published: January 2024

Background: Antepartum depression, with an incidence of 20.7%, is a pressing global public health concern due to its detrimental effects on both the physical and mental health of pregnant women, as well as the potential risk it poses for depression in their offspring. Nevertheless, there is a lack of consensus among existing studies regarding this issue. Here, we systematically evaluated the relationship between maternal perinatal depression and offspring depression by meta-analysis. Methods: We conducted a comprehensive search for relevant studies in Pubmed, Embase, The Cochrane Library, CNKI, Wanfang, VIP, and Chinese Biomedical Literature Service System databases. The prospective cohort studies, which were published in English or Chinese, reported the occurrence of maternal prenatal and/or postnatal depression within one year postpartum and assessed the subsequent development of depression in their offspring, were included. Study quality was assessed with the Newcastle-Ottawa Scale. Review Manager 5.4 software was used for meta-analysis. Subgroup analysis was performed. Publication bias was evaluated with a funnel plot. Results: Totally, 12 studies were included. The meta-analysis found that maternal perinatal depression increased the risk of offspring depression by 1.64 (95% confidence interval (95% CI): 1.37, 1.96, p < 0.001). Subgroup analysis showed that the risk of offspring depression was significantly increased in the European population with maternal perinatal depression (odds ratio (OR) = 1.90, 95% CI (1.49, 2.42), p < 0.001), but not in the Australian and the American populations. The combined effect sizes of maternal antepartum and postpartum depression were (OR = 1.70, 95% CI (1.27, 2.27), p < 0.001) and (OR = 1.74, 95% CI (1.31, 2.32), p < 0.001), respectively. The combined effect size of the relationship of maternal perinatal depression with offspring depression in childhood and adulthood was (OR = 1.70, 95% CI (1.28, 2.25), p < 0.001) and (OR = 1.60, 95% CI (1.27, 2.02), p < 0.001), respectively. The adjusted and unadjusted combined effect sizes were (OR = 1.44, 95% CI (1.14, 1.82), p < 0.001) and (OR = 1.97, 95% CI (1.49, 2.60), p < 0.001), respectively. There may be some publication bias in the included studies. Conclusions: Maternal perinatal depression is associated with an increased risk of depression in offspring. Effective prevention and management of depression in perinatal women is necessary to mitigate the risk of depression in offspring.
Cervical Stump Cancer after Subtotal Hysterectomy: A Retrospective Research of 127 Cases from China and Literature Review
Authors: Wang Jia , Zeng Xi , Min Lin , Li Lin
Published: January 2024

Background: Cervical stump cancer is a rare disease, which is subsequent to a previous subtotal hysterectomy. Among patients who underwent a subtotal hysterectomy, approximately 1%–3% develop cervical stump cancer which represents 3%–9% of all the cervical cancers. Methods: After acquiring consent from our ethics committee, we recruited the subjects and reviewed the patients’ data of those who were admitted to our hospital from January 2010 to December 2022. Written informed consent from all the study participants was acquired, and all materials complied with the Declaration of Helsinki and ethical standards. The patients’ data records, including clinical characteristics, treatment methods, human papillomavirus (HPV) infection conditions before the operation, complications of the treatment and follow-up status were analyzed. The HPV infection status was detected by Tellgen systems (Tellgen Corporation, Shanghai, China). SPSS software (Version 22.0, IBM Company, Armonk, NY, USA) was used for data analysis. Data is shown as mean ± standard deviation. A two-side p value < 0.05 was considered to be significant. Results: There were 127 cases with cervical stump cancer treated in our hospital during this period. The interval time between subtotal hysterectomy and stump cancer was 130.7 months. Vaginal bleeding, postcoital bleeding and pelvic pain were the main symptom. Seventy-two cases were squamous cancer and adenocarcinoma occurred in 39 cases. All patients received surgery or concurrent chemoradiotherapy. One hundred and ten cases were included in the follow-up. The median observation time was 65 months. Vaginal bleeding, gastrointestinal symptoms and vaginal contracture were the most common complications. The median observation time was 65 months and the 5-year disease-free rate for all patients was 51.8% with the 5-year overall survival for all patients being 77.3%. Conclusions: Subtotal hysterectomy results in a potential to develop cervical stump cancer. Cytological studies, cervical biopsy and endocervical curettage should be considered before a subtotal hysterectomy is performed. The patients should be well informed of the risk for retaining the cervical stump and further cervical stump cancer screening is mandatory.
A Cross Sectional Study of Second Trimester Sonographically Diagnosed Low-Lying Placenta and Associated Maternal and Neonatal Outcomes at Delivery
Authors: Charron Bethany L. , Maxwell Rose A. , McKenna David S.
Published: January 2024

Background: The optimal management of patients diagnosed in the mid-gestation with a low-lying placenta (LLP) is controversial. We sought to determine the rate of adverse pregnancy outcomes with an initial diagnosis of LLP, and whether this was dependent on a follow up sonographic diagnosis of resolution or the initial placenta-to-internal os distance (P-IOD). Methods: A retrospective cross-sectional study of singleton pregnancies with a sonographically diagnosed LLP between 18–24 weeks’ gestation (12/2010 to 7/2018) was conducted at a tertiary referral center in the U.S. Follow-up ultrasound examinations from the late second or early third trimester were reviewed. Maternal morbidity associated with blood loss, regardless of resolution of LLP was recorded and stratified by P-IOD at diagnosis. The LLP was considered resolved if the P-IOD was ≥2.0 cm by 34 weeks’ gestation . Proportions of resolution, admissions for antepartum bleeding, preterm delivery, mode of delivery, neonatal morbidity and preterm delivery were obtained. Data was analyzed by comparing categorical variables via Chi-squared test, and continuous variables using Student t-test and analysis of variance (ANOVA). Results: Five hundred three pregnancies met inclusion criteria. All except two LLPs resolved by 34 weeks’ gestation (99.6% resolution rate). There were 40 patients who did not have a follow up ultrasound. Overall rates of hemorrhage and blood transfusion were greater than the general population. The rate of maternal hemorrhage between resolved, unresolved, unknown groups, and initial P-IOD was not significantly different. The odds of admission for antepartum bleeding were significantly greater if the P-IOD was <0.5 cm. An increase in neonatal acidosis was found in the group with initial P-IOD <0.5 cm, despite 100% resolution at time of delivery. Conclusions: The diagnosis of an LLP at 18–24 weeks’ gestation despite a high rate of resolution, is associated with an increased risk for maternal hemorrhage. LLP may be an independent risk factor for hemorrhage, regardless of the initial P-IOD or resolution. Clinicians and patients should be aware of this risk and prepared to manage adverse events.
The Potential Role of GJA1 and SPP1 Expressed by the Endometrium Based on Single Cell Transcriptome Analysis in Endometrial Infertility
Authors: Lu Zhenzhen , Tang Qianqian , Chen Chunyan , Zhao Xiaojie , Gao Ying , Wei Qiongqiong
Published: January 2024

Background: Endometrial infertility accounts for a significant proportion of infertility cases, and single-cell transcriptome data have revealed that hub genes may play an important role during pregnancy. Methods: Based on the endometrial single-cell sequencing data from National Center for Biotechnology Information (NCBI) database, we performed clustering, staging, and functional analyses to screen and validate key genes affecting endometrial infertility. Results: Through bioinformatics analysis, we found that the proportion of ciliated cells peaked from the early to mid secretory phase, ciliary motility decreased in the mid secretory phase, while the hub gene that connexin 43 (GJA1) and secreted phosphoprotein 1 (SPP1) expressed in the endometrium may determine successful pregnancy. In immunohistochemistry validation, GJA1 and SPP1 were significantly highly expressed in the endometrium of a normal pregnancy, compared to recurrent miscarriage. Similarly, GJA1 and SPP1 were expressed higher in the fetal villus of a normal pregnancy as compared to recurrent miscarriage, while no difference was found in the decidua. CellPhoneDB and protein–protein interactions (PPIs) indicated an interaction among notch receptor 1 (NOTCH1), GJA1 and SPP1. Conclusions: GJA1 and SPP1 exhibit higher expression levels in the endometrium and fetal villus of a normal pregnancy as compared to recurrent miscarriage, suggesting that GJA1 and SPP1 may play a pivotal role in endometrial infertility.
Genome-Wide Identification of R2R3-MYB Family Genes and Their Response to Stress in Dendrobium nobile
Authors: Wu Liping , Fan Jizhou , Su Xinglong , Peng Daiyin , Xing Shihai
Published: January 2024

Background: R2R3-MYB genes comprise one of the largest and most important gene families in plants, and are involved in the regulation of plant growth and development as well as responses to abiotic stresses. However, the functions of R2R3-MYB genes in Dendrobium nobile remains largely unknown. Methods: Here, a comprehensive genome-wide analysis of D. nobile R2R3-MYB genes was performed, in which phylogenic relationships, gene structures, motif composition, chromosomal locations, collinearity analysis, and cis-acting elements were investigated. Moreover, the expression patterns of selected DnMYB genes were analyzed in various tissues and under different abiotic stresses. Results: In total, 125 DnMYB genes were identified in the D. nobile genome, and were subdivided into 26 groups based on phylogenetic analysis. Most genes in the same subgroup showed similar exon/intron structure and motif composition. All the DnMYB genes were mapped to 19 chromosomes with the co-linearity relationship. Reverse transcription-quantitative real-time PCR (RT-qPCR) results showed that 8 DnMYBs exhibited different expression patterns in different plant tissues, and were differentially expressed in response to abscisic acid, methyl jasmonate, low-temperature stress. Conclusions: This work contributes to a comprehensive understanding of the R2R3-MYB gene family in D. nobile, and provides candidate genes for future research on abiotic stress in this plant.
Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer
Authors: Cheng Yanan , Dong Li , Bu Dechao , Han Lei , Zhao Yi , Liu Juntian , Guo Xiaojing , Xu Hanli , Yu Jinpu
Published: January 2024

Background: Structural variations (SVs) are common genetic alterations in the human genome. However, the profile and clinical relevance of SVs in patients with hereditary breast and ovarian cancer (HBOC) syndrome (germline BRCA1/2 mutations) remains to be fully elucidated. Methods: Twenty HBOC-related cancer samples (5 breast and 15 ovarian cancers) were studied by optical genome mapping (OGM) and next-generation sequencing (NGS) assays. Results: The SV landscape in the 5 HBOC-related breast cancer samples was comprehensively investigated to determine the impact of intratumor SV heterogeneity on clinicopathological features and on the pattern of genetic alteration. SVs and copy number variations (CNVs) were common genetic events in HBOC-related breast cancer, with a median of 212 SVs and 107 CNVs per sample. The most frequently detected type of SV was insertion, followed by deletion. The 5 HBOC-related breast cancer samples were divided into SVhigh and SVlow groups according to the intratumor heterogeneity of SVs. SVhigh tumors were associated with higher Ki-67 expression, higher homologous recombination deficiency (HRD) scores, more mutated genes, and altered signaling pathways. Moreover, 60% of the HBOC-related breast cancer samples displayed chromothripsis, and 8 novel gene fusion events were identified by OGM and validated by transcriptome data. Conclusions: These findings suggest that OGM is a promising tool for the detection of SVs and CNVs in HBOC-related breast cancer. Furthermore, OGM can efficiently characterize chromothripsis events and novel gene fusions. SVhigh HBOC-related breast cancers were associated with unfavorable clinicopathological features. SVs may therefore have predictive and therapeutic significance for HBOC-related breast cancers in the clinic.
Protein Signatures for Distinguishing Colorectal Cancer Liver Metastases from Primary Liver Cancer Using Tissue Slide Proteomics
Authors: Zhou Xiaoman , Wang Xiuyuan , Bai Ruizhen , Li Hanjie , Hua Dong , Gao Xiao-Dong , Yang Ganglong , Liu Quan
Published: January 2024

Background: Colorectal cancer liver metastasis (CRLM) and hepatocellular carcinoma (HCC) are both high incidence tumors in China. In certain poorly differentiated cases they can exhibit comparable imaging and pathological characteristics, which impedes accurate clinical diagnosis. The use of protein-based techniques with tissue slides offers a more precise means to assess pathological changes and has the potential to assist with tumor diagnosis. Methods: A simple in situ protein digestion protocol was established for protein fingerprint analysis of paraffin-embedded tissue slide samples. Additionally, machine learning techniques were employed to construct predictive models for CRLM and HCC. The accuracy of these models was validated using tissue slides and a clinical database. Results: Analysis of differential protein expression between CRLM and HCC groups reliably identified 977 proteins. Among these, 53 were highly abundant in CRLM samples and 57 were highly abundant in HCC samples. A prediction model based on the expression of six proteins (CD9, GSTA1, KRT20, COL1A2, AKR1C3, and HIST2H2BD) had an area under curve (AUC) of 0.9667. This was further refined to three proteins (CD9, ALDH1A1, and GSTA1) with an AUC of 0.9333. Conclusions: Tissue slide proteomics can facilitate accurate differentiation between CRLM and HCC. This methodology holds great promise for improving clinical tumor diagnosis and for identifying novel markers for challenging pathological specimens.
Parkinson's Disease Diagnosis Using miRNA Biomarkers and Deep Learning
Authors: Kumar Alex , Kouznetsova Valentina L. , Kesari Santosh , Tsigelny Igor F.
Published: January 2024

Background: The current standard for Parkinson’s disease (PD) diagnosis is often imprecise and expensive. However, the dysregulation patterns of microRNA (miRNA) hold potential as a reliable and effective non-invasive diagnosis of PD. Methods: We use data mining to elucidate new miRNA biomarkers and then develop a machine-learning (ML) model to diagnose PD based on these biomarkers. Results: The best-performing ML model, trained on filtered miRNA dysregulated in PD, was able to identify miRNA biomarkers with 95.65% accuracy. Through analysis of miRNA implicated in PD, thousands of descriptors reliant on gene targets were created that can be used to identify novel biomarkers and strengthen PD diagnosis. Conclusions: The developed ML model based on miRNAs and their genomic pathway descriptors achieved high accuracies for the prediction of PD.
ARHGAP6 Suppresses Breast Cancer Tumor Growth by Promoting Ferroptosis via RhoA-ROCK1-p38 MAPK Signaling
Authors: Chen Xiaoqing , Zhu Jing , Li Xiangzhi , Chen Jintao , Zhou Zhisheng , Fan Xulong , Liang Ruijian , Liu Haiyan , Zhu Dajiang
Published: January 2024

Background: Ferroptosis, a distinct iron-dependent form of regulated cell death, is induced by severe lipid peroxidation due to reactive oxygen species (ROS) generation. Breast cancer patient survival is correlated with the tumor-suppressing properties of Rho guanosine triphosphatase hydrolase enzyme (GTPase)-activating protein 6 (ARHGAP6). This study investigates the impact and mechanisms of ARHGAP6 on ferroptosis in breast cancer. Methods: Using quantitative RT-PCR, Western blotting, and immunofluorescence staining, ARHGAP6 expression was detected in a gene expression dataset, cancer tissue samples, and cells. ARHGAP6 was overexpressed or silenced in breast cancer cell lines. Cell proliferation was measured using 5-ethynyl-2-deoxyuridine (EdU) assay, and cell death rate was determined using LDH cytotoxicity assay. As indicators of ferroptosis, Fe2+ ion content, lipid ROS, glutathione peroxidase 4 (GPX4), ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1), prostaglandin-endoperoxide synthase 2 (PTGS2), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were evaluated. Results: ARHGAP6 was obviously downregulated in cancer tissues and cells. ARHGAP6 overexpression decreased cell proliferation, elevated cell death and lipid ROS, decreased GPX4 and SLC7A11, increased PTGS2, ACSL4, and CHAC1, and inhibited RhoA/ROCK1 and p38 MAPK signaling in cancer cells. ARHGAP6 knockdown exerted opposite effects to those of ARHGAP6 overexpression. p38 signaling suppression reversed the effect of ARHGAP6 knockdown on ferroptosis, while RhoA/ROCK1 signaling inhibition compromised the effect of ARHGAP6 on p38 MAPK signaling. In mice models, ARHGAP6 together with the ferroptosis inducer RSL3 cooperatively enhanced ferroptosis and inhibited tumor growth of cancer cells. ARHGAP6 mRNA level was positively correlated with that of ferroptosis indicators in tumor tissues. Conclusions: This study revealed that ARHGAP6 inhibited tumor growth of breast cancer by inducing ferroptosis via RhoA/ROCK1/p38 MAPK signaling. Integrating ARHGAP6 with ferroptosis-inducing agents may be a promising therapeutic strategy for breast cancer treatment.
Association of 10 Genetic Variations and 10 Environmental Factors with Myopia of Different Severities in Different Age Groups of People in Northeast China
Authors: Sun Yan , Li Zhuang , Wang Zhuoshi , He Xingru , Yu Sile , Hu Lan , Xu Ling , He Wei
Published: January 2024

Background: To investigate the association of 10 genetic variations and 10 environmental factors with myopia of different severities in different age groups of children and adolescents in northeast China. Methods: Parental history and genetic testing for myopia-related susceptibility genes were carried out in a cohort of children and adolescents aged 2–17 years. In addition, 10 single nucleotide polymorphism (SNP) sites for genotyping and 10 environmental risk factors were selected, and the differences between site variation and environmental factors in different age groups with different degrees of myopia were explored. Results: A total of 2497 volunteers were recruited, including 2023 myopes and 474 non-myopes in the control group. From the cohort, 1160 subjects were sequenced for myopia SNP sites. Compared with the non-myopic group, the myopia of parents, outdoor activity less than 60 min per day, and a high-sugar diet were risk factors for developing myopia. Two syntrophin beta 1 (SNTB1) sites, rs4455882 and rs6469937 were found to be significantly associated with moderate myopia; fibroblast growth factor 10 (FGF10) rs339501 was significantly correlated with high myopia; and insulin-like growth factor 1 (IGF1) rs5742714 was significantly correlated with different degrees of myopia in the age group of <6 years. Finally, the FGF10 gene rs339501 SNP was significantly associated with moderate myopia and mild myopia in the 6- to 12-year-old age group. Conclusions: Our results indicate that myopia is affected by both environmental and genetic factors. To prevent and control myopia, attention should be paid to the parental history of myopia, a high-sugar diet should be avoided, and outdoor time should be adjusted according to the average daily sunshine. In addition, it is necessary to pay attention to the increased risk of myopia in school-age children caused by SNTB1 rs4455882, FGF10 rs339501, and IGF1 rs5742714.
Role of SLC5A8 as a Tumor Suppressor in Cervical Cancer
Authors: Vargas-Sierra Orlando , Hernández-Juárez Jennifer , Uc-Uc Perla Yaceli , Herrera Luis A , Domínguez-Gómez Guadalupe , Gariglio Patricio , Díaz-Chávez José
Published: January 2024

Background: The SLC5A8 gene is silenced in various types of cancer, including cervical cancer; we recently demonstrated that the SLC5A8 gene is also silenced in cervical cancer by hypermethylation of the CpG island in the gene promoter. This study aims to analyze whether SLC5A8 could be a tumor suppressor in cervical cancer. Methods: After ectopic expressing SLC5A8 in the HeLa cell line, we evaluated its effects on cell behavior both in vitro and in vivo by Confocal immunofluorescence, cell proliferation, migration assays, and xenograft transplants. Results: Overexpression of SLC5A8 in the HeLa cell line decreased its proliferation by arresting cancer cells in the G1 phase and inhibiting cellular migration. Furthermore, we observed that pyruvate increased the SLC5A8 effect, inducing S-phase arrest and inhibiting the entry into mitosis. SLC5A8 decreased tumor growth in xenograft transplants, significantly reducing the volume and tumor weight at 35 days of analysis. Conclusions: In summary, our results indicate that SLC5A8 has a role as a tumor suppressor in cervical cancer.
Polycystic Ovary Syndrome Pathophysiology: Integrating Systemic, CNS and Circadian Processes
Authors: Anderson George
Published: January 2024

The conceptualization of polycystic ovary syndrome (PCOS) has primarily focused on hormonal alterations driven by changes within the hypothalamus and ovarian granulosa cells, with treatment by the contraceptive pill and weight loss. However, a growing body of data implicates wider systemic and central nervous system (CNS) changes in the pathoetiology and pathophysiology of PCOS, with consequent implications for targeted treatments. It is proposed that there is a significant role for night-time interactions of factors acting to regulate whether the rising level of cortisol over the night and during the morning cortisol awakening response (CAR) is able to induce the nuclear translocation of the glucocorticoid receptor (GR), thereby influencing how the immune and glial systems regulate cellular function in preparation for the coming day. Factors affording protection in PCOS also inhibit GR nuclear translocation including gut microbiome-derived butyrate, and pineal/local melatonin as well as melatonin regulated bcl2-associated athanogene (BAG)-1. A significant pathophysiological role in PCOS is attributed to the aryl hydrocarbon receptor (AhR), which shows heightened levels and activity in PCOS. The AhR is activated by ligands of many systemic processes, including white adipocyte-derived kynurenine, implicating obesity in the pathophysiological changes occurring in the hypothalamus and ovaries. AhR activation has consequences for the physiological function in the hypothalamic paraventricular nucleus, granulosa cells and adipocytes, partly mediated by AhR upregulation of the mitochondrial N-acetylserotonin/melatonin ratio, thereby decreasing melatonin availability whilst increasing local stress plasticity in the paraventricular nucleus. This article reviews in detail the wider systemic and CNS changes in PCOS highlighting interactions of local and pineal melatonergic pathway, gut microbiome-derived butyrate, white adipocyte-derived kynurenine, the hypothalamic paraventricular nucleus tanycytes/astrocytes, and the hypothalamus-pituitary-adrenal (HPA) axis driven glucocorticoid receptor activation in PCOS pathophysiology. This integrates a wide array of previously disparate data on the biological underpinnings of PCOS, including how PCOS associates with many other currently classified medical conditions, such as depression, bipolar disorder, type 1 diabetes mellitus and the autism spectrum. Numerous future research and treatment implications are detailed.
The Centrosomes of Haploid and Diploid Cells Have an Equal Number of Centrioles in the Parasitoid Wasp Anisopteromalus Calandrae
Authors: Uzbekov Rustem , N'goran San-Whouly Mauricette Ouali , Garanina Anastasiia , Pancione Massimo , Chaika Stanislav Yu. , Bressac Christophe
Published: January 2024

Background: The centrosome is the main center of the organization of microtubules (MT) in the cell, the origin for the formation of flagella and cilia, as well as the site of many regulatory intracellular processes. In diploid cells, the centrosome includes two centrioles connected to some additional structures and surrounded by pericentriolar material. Methods: The ultrastructure of the cells was studied using transmission electron microscopy on serial ultrathin sections. Results: Here, using transmission electron microscopy on a complete series of ultrathin sections of the centrosome region, we studied the relation between the number of centrioles and ploidy in diploid cells of female wasps and haploid cells of male in the parasitoid wasp Anisopteromalus calandrae (Hymenoptera). It showed that the haploid cells of the male insect have the same number of centrioles as the diploid cells of the female. Conclusions: It can be concluded that there is no strict correlation between the number of chromosome sets (ploidy) and the number of centrioles in haplodiploid insects.
Autophagy, Ferroptosis, Apoptosis and Pyroptosis in Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Zhao Shuangshuang , Guo Yan , Yin Xunzhe
Published: January 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) has a global prevalence of 25% and is a leading cause of cirrhosis and hepatocellular carcinoma. The prevalence of MASLD has been increasing, mirroring the global increase in diabetes and metabolic syndrome. MASLD is a chronic and progressive condition characterized by inflammation, oxidative stress, insulin resistance, and disruptions in lipid metabolism. Programmed cell death (PCD) plays a pivotal role in determining the pathological aspects of MASLD, including liver inflammation, fibrosis, and even the potential for malignant transformation. PCD is a dominant process that is fundamental for eukaryotic growth and serves as a regulatory factor in MASLD. PCD encompasses various pathways, including autophagy, ferroptosis, apoptosis, and pyroptosis. These PCD pathways can be activated at different stages of MASLD. The key effector molecules involved in these processes are central focal points in the development of therapeutic interventions for MASLD. Here, we comprehensively review the idea that targeted the modulation of the PCD pathway may be an effective approach for the prevention and/or treatment of MASLD.
N6-Methyladenosine Regulator-Mediated Methylation Modification Patterns with Distinct Prognosis, Oxidative Stress, and Tumor Microenvironment in Renal Cell Carcinoma
Authors: Li Chunyang , Zhu Maoshu , Gao Chuane , Lu Fuhua , Chen Huoshu , Liu Jiancheng , Zhong Weimin
Published: January 2024

Objective: Emerging evidence suggests the biological implications of N6-methyladenosine (m6A) in carcinogenesis. Herein, we systematically analyzed the role of m6A modification in renal cell carcinoma (RCC) progression. Methods: Based on 23 m6A regulators, unsupervised clustering analyses were conducted to determine m6A modification subtypes across 893 RCC specimens in the Cancer Genome Atlas (TCGA) cohort. By performing principal component analysis (PCA) analysis, m6A scoring system was developed for evaluating m6A modification patterns of individual RCC patients. The activity of signaling pathways was assessed by gene-set variation analysis (GSVA) algorithm. The single-sample gene set enrichment analysis (ssGSEA) algorithm was applied for quantifying the infiltration levels of immune cells and the activity of cancer immunity cycle. Drug responses were estimated by genomics of drug sensitivity in cancer (GDSC), the Cancer Therapeutics Response Portal (CTRP) and Preservice Research Institute for Science and Mathematics (PRISM) database. databases. Results: Five m6A modification subtypes were characterized by different survival outcomes, oxidative stress, cancer stemness, infiltrations of immune cells, activity of cancer immunity cycle, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression and microsatellite instability (MSI) levels. According to m6A score, RCC patients were categorized into high and low m6A score groups. Patients with high m6A score displayed a prominent survival advantage, and the prognostic value of m6A score was confirmed in two anti-PD-1/PD-L1 immunotherapy cohorts. m6A score was significantly linked to oxidative stress-related genes, and high m6A score indicated the higher sensitivity to axitinib, pazopanib and sorafenib and the lower sensitivity to sunitinib. Conclusion: This study analyzed the extensive regulatory mechanisms of m6A modification on oxidative stress, the tumor microenvironment, and immunity. Quantifying m6A scores may enhance immunotherapeutic effects and assist in developing more effective agents.
Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells
Authors: Ma Min , Ge Jian-Yun , Nie Yun-Zhong , Li Yu-Mei , Zheng Yun-Wen
Published: January 2024

Establishing reliable and reproducible animal models for disease modelling, drug screening and the understanding of disease susceptibility and pathogenesis is critical. However, traditional animal models differ significantly from humans in terms of physiology, immune response, and pathogenesis. As a result, it is difficult to translate laboratory findings into biomedical applications. Although several animal models with human chimeric genes, organs or systems have been developed in the past, their limited engraftment rate and physiological functions are a major obstacle to realize convincing models of humans. The lack of human transplantation resources and insufficient immune tolerance of recipient animals are the main challenges that need to be overcome to generate fully humanized animals. Recent advances in gene editing and pluripotent stem cell-based xenotransplantation technologies offer opportunities to create more accessible human-like models for biomedical research. In this article, we have combined our laboratory expertise to summarize humanized animal models, with a focus on hematopoietic/immune system and liver. We discuss their generation strategies and the potential donor cell sources, with particular attention given to human pluripotent stem cells. In particular, we discuss the advantages, limitations and emerging trends in their clinical and pharmaceutical applications. By providing insights into the current state of humanized animal models and their potential for biomedical applications, this article aims to advance the development of more accurate and reliable animal models for disease modeling and drug screening.
Posttraumatic Basal Ganglia Infarction by Lenticulostriate Artery Injury in Adult Patients: A Review
Authors: Moon Jong Un , Kim Younghwan , Kim Mina , Kim Myoung Soo
Published: January 2024

Post-traumatic striatocapsular infarction (SCI) due to lenticulostriate artery (LSA) damage is rare. Most cases reported are in children. We discuss the pathogenesis and differential diagnosis of this kind of SCI after trauma in adult patients. The most common etiology of non-traumatic SCI are an embolism from the proximal artery, cardiogenic embolism, and atherosclerotic plaque in the proximal middle cerebral artery (MCA). However, injury of the LSA after trauma may lead to hemorrhagic infarction in the basal ganglia (BG). Post-traumatic SCI due to LSA damage might be associated with hemorrhage in the BG. The main locations of these lesions are the distal perfusion area of the LSA, similar to SCI due to intracranial atherosclerotic disease affecting the MCA. Vessel wall imaging, magnetic resonance angiography, and ultrahigh-resolution computed tomography can be used for differentiating the injury mechanism in SCI following a traumatic event.
Efficacy of Noninvasive Brain Stimulation in Treating General Psychopathology Symptoms in Schizophrenia: A Meta-Analysis
Authors: Huang Wenqian , Wang Hong , Hu Na , Chai Jiabao , Zhou Xuanzi , Liu Fuquan , Li Ying
Published: January 2024

Objectives: Noninvasive brain stimulation (NIBS) has been shown to effectively alleviate negative and positive symptoms in patients with schizophrenia. However, its impact on depressive symptoms and general psychopathology symptoms (GPSs), which are crucial for functional outcomes, remains uncertain. We aimed to compare the efficacy of various NIBS interventions in treating depressive symptoms and GPSs. Methods: We conducted a comprehensive search of multiple databases and performed a meta-analysis to evaluate the efficacy of NIBS in treating depressive symptoms and GPSs in schizophrenia. The effect sizes of NIBS for depression symptoms and GPSs were estimated using standard mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses were employed to examine potential influencing factors on the pooled SMD of NIBS for GPSs. Results: Our search yielded 35 randomized controlled trials involving 1715 individuals diagnosed with schizophrenia. The protocol of this systematic review was registered with INPLASY (protocol ID: INPLASY202320082). Neither repetitive transcranial magnetic stimulation (rTMS) nor transcranial direct current stimulation (tDCS) demonstrated significant improvements in depressive symptoms compared to sham controls. NIBS exhibited a small-to-moderate effect size for GPSs, with a pooled SMD of –0.2956 (95% CI: –0.459 to –0.132) and a heterogeneity (I2) of 58.9% (95% CI: 41.5% to 71.1%; p < 0.01) based on a random-effects model. Subgroup analyses of different types of NIBS, different frequencies of rTMS, and different stimulation sites of rTMS revealed no significant differences. Only sex had a significant influence on the effect size of NIBS for general psychopathology symptoms (p < 0.05). However, rTMS might be superior to tDCS, and high-frequency rTMS outperformed low-frequency rTMS in treating GPSs. Conclusions: We found a small-to-moderate effect size of NIBS in alleviating GPSs in patients with schizophrenia. Both rTMS and tDCS were more effective than sham stimulation in reducing GPSs in schizophrenia. The frequency used was associated with rTMS efficacy for GPSs.
Subclinical Neck Pain Leads to Differential Changes in Early Somatosensory Evoked Potentials in Response to a Novel Force Matching Tracking Task
Authors: Ambalavanar Ushani , Yielder Paul , McCracken Heather S. , Tabbert Hailey , Murphy Bernadette
Published: January 2024

Background: Neural adaptions in response to sensorimotor tasks are impaired in those with untreated, recurrent mild-to-moderate neck pain (subclinical neck pain (SCNP)), due to disordered central processing of afferent information (e.g., proprioception). Neural adaption to force modulation, a sensorimotor skill reliant on accurate proprioception, is likely to be impaired in those with SCNP. This study examined changes in somatosensory evoked potential (SEP) peak amplitudes following the acquisition of a novel force matching tracking task (FMTT) in those with SCNP compared to non-SCNP. Methods: 40 (20 female (F) & 20 male (M); average age (standard deviation, SD): 21.6 (3.01)) right-handed participants received controlled electrical stimulation at 2.47 Hz and 4.98 Hz (averaged 1000 sweeps/frequency) over the right-median nerve, to elicit SEPs before and after FMTT acquisition. Participants used their right thumb to match a series of force profiles that were calibrated to their right thumb (abductor pollicis brevis muscle) strength. To determine if motor learning was impacted, retention was assessed 24 to 48 hours later. Outliers were removed before running independent t-tests on normalized SEP peak amplitudes, and repeated measures analysis of variance (ANOVA) with planned contrasts on absolute and normalized motor performance accuracy. Benjamini-hochberg test was used to correct for multiple independent SEP comparisons. Results: SEP peaks: N18 (t(29.058) = 2.031, p = 0.026), N20 (t(35) = –5.460, p < 0.001), and P25 (t(33) = –2.857, p = 0.004) had group differences. Motor performance: Absolute error (n = 38) had a main effect of time, and significant pre-and post-acquisition contrast for time (both p < 0.001). Conclusions: Group differences in the olivary-cerebellar pathway (N18), and cortical processing at the somatosensory cortex (N20 and P25), suggests that SCNP alters cortical and cerebellar processing compared to non-SCNP in response to FMTT acquisition. The sensory-motor integration differences in the SCNP group suggests that those with SCNP may rely more on feedback loops for discrete sensorimotor tasks dependent on proprioception. Early SEP changes may be used as a marker for altered neuroplasticity in the context of motor skill acquisition of a novel discrete FMTT in those with SCNP.
Acute Changes in the Resting Brain Networks in Concussion Patients: Small-World Topology Perspective
Authors: Kuang Hong-mei , Chen Yan , Huang Ji-lan , Li Jian , Zhang Ning , Ai Hong-hui , Xia Guo-jin
Published: January 2024

Background: The acute changes that occur in the small-world topology of the brain in concussion patients remain unclear. Here, we investigated acute changes in the small-world organization of brain networks in concussion patients and their influence on persistent post-concussion symptoms. Methods: Eighteen concussion patients and eighteen age-matched controls were enrolled in this study. All participants underwent computed tomography, magnetic resonance imaging (MRI), susceptibility weighted imaging, and blood oxygen level-dependent functional MRI. A complex network analysis method based on graph theory was used to calculate the parameters of small-world networks under different degrees of network sparsity. All subjects were evaluated using the Glasgow Coma Scale and Rivermead Postconcussion Symptom Questionnaire. Results: Compared with the controls, the normalized cluster coefficient (γ) of whole brain networks in patients and the “small-world” index (σ) was slightly enhanced, whereas the standardized minimum path (λ) was slightly shorter. Whole brain effect (Eglobal) and local effect (Elocal) changes were not pronounced. Under the condition of minimum network sparsity (Dmin = 0.13), the numbers of nodes in the “right intraorbital superior frontal gyrus” (Anatomical Automatic Labeling, AAL26), right globus pallidus (AAL76), and bilateral temporal transverse gyrus (AAL79,80) in brain concussion patients were significantly lower. The numbers of nodes in the left subcapital lobe (AAL61) and left occipital gyrus (AAL51) were significantly higher, and the normalized cluster coefficients of the right intraorbital supraphalus (AAL26) and left posterior cingulate gyrus (AAL35) were significantly increased. The normalized clustering coefficients of the right triangular subfrontal gyrus (AAL55) (based on the normalized clustering coefficients of nodes in AAL14) and left sub-parietal lobes (AAL61) were significantly reduced. The mean local effects of nodes in the right intraorbital upper frontal gyrus (AAL26), left posterior cingulate gyrus (AAL35), and bilateral auxiliary motor cortex (AAL19, 20) were enhanced, whereas the mean local effects of the bilateral triangular inferior frontal gyrus (AAL13,14) and left insular cap (AAL11) were reduced (p < 0.05). Conclusions: The overall trend of network topology abnormalities in patients was random, and generalized and local functional abnormalities were seen. Changes in the function and affective circuitry of the resting default network were particularly pronounced in these patients, which we speculate may be one of the main drivers of the cognitive dysfunction and mood changes seen in concussion patients.
The Association between Assisted Reproductive Technologies and Neurodevelopmental Disorders in Offspring: An Overview of Current Evidence
Authors: Zeng Zhitao , Wang Zhuoyi , Yu Pengfei , Wang Yuchen , Pei Yuqiang , Dai Yujuan , Liu Yanping , Yang Ye
Published: January 2024

The utilization of assisted reproductive technologies (ART) is on the rise, resulting in a growing population of ART-conceived offspring. The health concerns of this unique population have attracted significant attention. During ART procedures, gametes and early-stage embryos are exposed to various non-physiological conditions, such as manipulation, culture media, and cryopreservation, which may disrupt embryonic development and potentially impact the health of offspring. Notably, the potential impact of ART on neurodevelopment and its association with an increased risk of neurodevelopmental disorders (NDD) later in life remains a subject of debate. This review aims to summarize the current research advancements concerning the effects of ART on neurodevelopment, specifically focusing on the evidence of the relationship between ART, epigenetic modifications, and NDD, including autism spectrum disorder, intellectual disability, attention deficit hyperactivity disorder, and cerebral palsy. Future studies should prioritize large sample sizes, rigorous adjustment for confounding factors, and the use of interdisciplinary approaches to effectively monitor the neurodevelopmental outcomes of ART-conceived children.
Puerarin Attenuates Cycloheximide-Induced Oxidative Damage and Memory-Consolidation Impairment in Rats
Authors: Wu Kuo-Jen , Lien Jin-Cherng , Wu Chi-Rei
Published: January 2024

Background: Cycloheximide (CXM), an antifungal antibiotic, causes impaired memory consolidation as a side effect partially by disturbing the activities of the central catecholaminergic and cholinergic system. Some reports indicated that puerarin prevented memory impairment in various models in rodents. However, the protective effects of puerarin on the side effects of cycloheximide for memory consolidation impairment have not yet been investigated. Methods: The protective effects of puerarin on CXM-induced memory-consolidation impairment, and memory impairment produced by central administration of AF64A neurotoxin, were investigated using a passive avoidance task in rats. A combination of transmitter receptor agonists and antagonists was used to explore the effects of puerarin on nervous system function. The activity of antioxidant defense systems and neurotransmitter systems in the prefrontal cortex and hippocampus were assayed. Results: Systemic (25 and 50 mg/kg, i.p.) or central (5 and 10 µg/brain, i.c.v.) administration of puerarin attenuated CXM-induced memory-consolidation impairment produced by 1.5 mg/kg CXM (s.c.) in rats. The improvements produced by 50 mg/kg puerarin were blocked by cholinergic antagonists, a 5-HT2 receptor agonist, and an adrenergic receptor antagonist. Puerarin (only at 50 mg/kg, i.p.) reversed the CXM-induced alterations of the levels of norepinephrine in the prefrontal cortex and the levels of monoamines in the hippocampus. Puerarin also increased antioxidant-defense-system activities in the prefrontal cortex and hippocampus, which had been decreased by CXM. Conclusions: We suggested that the attenuating effects of puerarin on CXM-induced memory-consolidation impairment may be due to decrease oxidative damage and the normalition of the neurotransmitter function in the prefrontal cortex and hippocampus.
Measures to Prevent Infection in Cardiac Implantable Electronic Device Replacements or Upgrades
Authors: Hoyos Carolina , Qian Xiaoxiao , Matos Carlos D. , Gabr Mohamed , Hincapie Daniela , Cadigan John B. , Steiger Nathaniel , Diaz Juan C. , Sauer William , Romero Jorge E.
Published: January 2024

Cardiac implantable electronic device (CIED) infections represent one of the most threatening complications associated with device implantation, due to an increase in morbidity and mortality rates, as well as healthcare costs. Besides, it is important to highlight that when compared to the initial implantation of a device, the risks associated with procedures like generator changes, lead and pocket revisions, or device upgrades double. Consequently, to address this issue, various scoring systems, like the PADIT (Prior Procedures, Age, Depressed Renal Function, Immunocompromised Status, Type of Procedure), the RI-AIAC (Ricerca Sulle Infezioni Associate a ImpiAnto o Sostituzione di CIED), and the Shariff score, along with predictive models, have been developed to identify patients at a greater risk of infection. Moreover, several interventions have been assessed to evaluate their role in infection prevention ranging from improving skin preparation and surgical techniques to considering alternative strategies such as the subcutaneous Implantable Cardioverter-Defibrillator (ICD). Methods like antimicrobial prophylaxis, pocket irrigation, chlorhexidine gluconate pocket lavage, capsulectomy, and the use of antibacterial envelopes have been also explored as preventive measures. In this review, we provide a comprehensive assessment of CIED infections in patients undergoing repeat procedures and the strategies designed to reduce the risk of these infections.