Integrated transcriptomic analysis and machine learning for characterizing diagnostic biomarkers and immune cell infiltration in fetal growth restriction.

Background: Fetal growth restriction (FGR) occurs in 10% of pregnancies worldwide. Placenta dysfunction, as one of the most common causes of FGR, is associated with various poor perinatal outcomes. The main objectives of this study were to screen potential diagnostic biomarkers for FGR and to evaluate the function of immune cell infiltration in the process of FGR. Methods: Firstly, differential expression genes (DEGs) were identified in two Gene Expression Omnibus (GEO) datasets, and gene set enrichment analysis was performed. Diagnosis-related key genes were identified by using three machine learning algorithms (least absolute shrinkage and selection operator, random forest, and support vector machine model), and the nomogram was then developed. The receiver operating characteristic curve, calibration curve, and decision curve analysis curve were used to verify the validity of the diagnostic model. Using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), the characteristics of immune cell infiltration in placental tissue of FGR were evaluated and the candidate key immune cells of FGR were screened. In addition, this study also validated the diagnostic efficacy of TREM1 in the real world and explored associations between TREM1 and various clinical features. Results: By overlapping the genes selected by three machine learning algorithms, four key genes were identified from 290 DEGs, and the diagnostic model based on the key genes showed good predictive performance (AUC = 0.971). The analysis of immune cell infiltration indicated that a variety of immune cells may be involved in the development of FGR, and nine candidate key immune cells of FGR were screened. Results from real-world data further validated TREM1 as an effective diagnostic biomarker (AUC = 0.894) and TREM1 expression was associated with increased uterine artery PI (UtA-PI) (p-value = 0.029). Conclusion: Four candidate hub genes (SCD, SPINK1, TREM1, and HIST1H2BB) were identified, and the nomogram was constructed for FGR diagnosis. TREM1 was not only associated with a variety of key immune cells but also correlated with increased UtA-PI. The results of this study could provide some new clues for future research on the prediction and treatment of FGR.

Construction and validation of log odds of positive lymph nodes (LODDS)-based nomograms for predicting overall survival and cancer-specific survival in ovarian clear cell carcinoma patients.

Background: Ovarian clear cell carcinoma (OCCC) is one of the special histologic subtypes of ovarian cancer. This study aimed to construct and validate log odds of positive lymph nodes (LODDS)-based nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Methods: Patients who underwent surgical treatment between 2010 and 2016 were extracted from the Surveillance Epidemiology and End Results (SEER) database and the data of OCCC patients from the First Affiliated Hospital of Dalian Medical University were used as the external validation group to test the validity of the prognostic model. The best-fitting models were selected by stepwise Cox regression analysis. Survival probability was calculated by the Kaplan-Meier method, and the differences in survival time between subgroups were compared using the log-rank test. Each nomogram's performance was assessed by the calibration plots, decision curve analysis (DCA), and receiver operating characteristics (ROC) curves. Results: T stage, distant metastasis, marital status, and LODDS were identified as significant risk factors for OS. A model with four risk factors (age, T stage, stage, and LODDS value) was obtained for CSS. Nomograms were constructed by incorporating the prognostic factors to predict 1-, 3- and 5-year OS and CSS for OCCC patients, respectively. The area under the curve (AUC) range of our nomogram model for OS and CSS prediction ranged from 0.738-0.771 and 0.769-0.794, respectively, in the training cohort. The performance of this model was verified in the internal and external validation cohorts. Calibration plots illustrated nomograms have good prognostic reliability. Conclusion: Predictive nomograms were constructed and validated to evaluate the OS and CSS of OCCC patients. These nomograms may provide valuable prognostic information and guide postoperative personalized care in OCCC.

From clinical management to personalized medicine: novel therapeutic approaches for ovarian clear cell cancer.

Ovarian clear-cell cancer is a rare subtype of epithelial ovarian cancer with unique clinical and biological features. Despite optimal cytoreductive surgery and platinum-based chemotherapy being the standard of care, most patients experience drug resistance and a poor prognosis. Therefore, novel therapeutic approaches have been developed, including immune checkpoint blockade, angiogenesis-targeted therapy, ARID1A synthetic lethal interactions, targeting hepatocyte nuclear factor 1ß, and ferroptosis. Refining predictive biomarkers can lead to more personalized medicine, identifying patients who would benefit from chemotherapy, targeted therapy, or immunotherapy. Collaboration between academic research groups is crucial for developing prognostic outcomes and conducting clinical trials to advance treatment for ovarian clear-cell cancer. Immediate progress is essential, and research efforts should prioritize the development of more effective therapeutic strategies to benefit all patients.

Metabolic syndrome and risk of ovarian cancer: a systematic review and meta-analysis.

Background: MetS is associated with greater morbidity and mortality in relation to a number of malignancies, but its association with ovarian cancer remains contested. The present study was a systematic review and meta-analysis of case-control and cohort studies examining the association between MetS and ovarian cancer risk. Methods: The study was registered on the PROSPERO platform in January 2023 (CRD42023391830). Up until February 13, 2023, a complete search was undertaken in PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials. On the basis of inclusion and exclusion criteria, eligible studies for meta-analysis were screened to determine the association between MetS and ovarian cancer risk. Results: Five studies were included in total, including three cohort studies and two case-control studies. Meta-analysis showed no significant correlation between metabolic syndrome and ovarian cancer (OR=1.29, 95% CI: 0.90-1.84). Significant heterogeneity (I2 = 92.6, P<0.05) existed between the included studies. We performed a subgroup analysis of the risk of bias and showed that only unadjusted stratification of risk of bias for smoking (OR= 3.19, 95% CI: 2.14-4.76) and hysterectomy (OR= 3.19, 95% CI: 2.14-4.76) demonstrated a relationship between metabolic syndrome and ovarian cancer risk. The meta-regression analysis revealed that smoking and hysterectomy excision were substantially linked with heterogeneity (p < 0.05). Conclusion: Our research revealed no statistically significant association between MetS and ovarian cancer risk. The prevalence of metabolic syndrome has highlighted the need of enhancing and controlling women's metabolic health. However, the evaluation of metabolic syndrome as a cancer risk factor may be deceptive and etiologically uninformative.

Two- and three-dimensional sonographic findings of harlequin ichthyosis: case report and literature review.

BACKGROUND: Harlequin ichthyosis (HI) is a rare skin disorder with extremely high lethality due to a mutation of the ABCA12 gene. Because of its rarity and the often-late onset, prenatal screening for HI is extremely difficult, and most pregnant women might easily miss the period for optimal examinations. OBJECTIVE: To summarize the sonographic features of HI for prenatal diagnostic purposes. METHODS: The authors describe a case of HI with no family history who was diagnosed by using prenatal ultrasound scanning. The sonographic features of HI and the clinical characteristics of pregnant women were summarized by searching relevant literature over nearly two decades. RESULTS: The unique sonographic presentations including peeling skin, clenched hands and clubfeet, ectropion, flat nose, fetal growth impairment, polyhydramnios and echogenic amniotic fluid may be primarily related to skin disorders in HI fetuses. The authors also identified a novel pathogenic ABCA12 gene mutation and explained the possible pathogenic mechanisms. STUDY LIMITATIONS: Caution should be exercised in summarizing disease characteristics because of the small number of cases, and the authors are faced with the possibility of incomplete case searching. CONCLUSIONS: HI has relatively unique sonographic features. Therefore, 2D-ultrasound combined with 3D-ultrasound may be an effective method for the prenatal diagnosis of HI. Moreover, a novel pathogenic ABCA12 gene mutation may provide important clues for future research on the etiology of HI. However, the authors consider that additional studies are needed to provide more evidence for prenatal diagnosis.

A Case Report of Retroperitoneal Ectopic Pregnancy After in vitro Fertilization-Embryo Transfer and Literature Review.

Background: Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy that can be life threatening. The pathogenesis of REP remains inconclusive and the diagnosis and treatment modalities are unclear. Case Presentation and Review of the Literature: A 27-year-old woman (gravida: 3; parturition: 0) underwent transvaginal ultrasound (TVS) 40 days after in vitro fertilization-embryo transfer (IVF-ET); no intrauterine gestational sac was detected. The patient was asymptomatic and had no abnormalities on physical examination. ß-HCG and progesterone were 18.210 mIU/mL and 10.891 ng/mL, respectively. Transabdominal ultrasound (TAS) showed that the gestational sac had implanted adjacent to the abdominal aorta and near a branch of the iliac artery. Laparoscopic exploration was performed under general anesthesia; intraoperative findings showed that the gestational sac was approximately 2.5 cm in diameter and in the same location as suggested by preoperative ultrasound. Histopathological examination confirmed the diagnosis of EP. On day three post-surgery, the levels of ß-HCG had fallen to 911 mIU/mL. We further systematically reviewed the REP cases reported in the English literature and performed a review on the diagnosis and treatment of REP. Conclusion: Clinicians should be alert to the occurrence of REP. Combined radiological examinations including ultrasonography (TAS and TVS), CT, and MRI are essential for the early diagnosis of REP. Once a definitive diagnosis is made, appropriate treatment should be administered immediately. Although there are cases of successful drug treatment described in the literature, surgery remains as the primary treatment option for REP.

Two- and three-dimensional sonographic findings of harlequin ichthyosis: case report and literature review

Abstract Background Harlequin ichthyosis (HI) is a rare skin disorder with extremely high lethality due to a mutation of the ABCA12 gene. Because of its rarity and the often-late onset, prenatal screening for HI is extremely difficult, and most pregnant women might easily miss the period for optimal examinations. Objective To summarize the sonographic features of HI for prenatal diagnostic purposes. Methods The authors describe a case of HI with no family history who was diagnosed by using prenatal ultrasound scanning. The sonographic features of HI and the clinical characteristics of pregnant women were summarized by searching relevant literature over nearly two decades. Results The unique sonographic presentations including peeling skin, clenched hands and clubfeet, ectropion, flat nose, fetal growth impairment, polyhydramnios and echogenic amniotic fluid may be primarily related to skin disorders in HI fetuses. The authors also identified a novel pathogenic ABCA12 gene mutation and explained the possible pathogenic mechanisms. Study limitations Caution should be exercised in summarizing disease characteristics because of the small number of cases, and the authors are faced with the possibility of incomplete case searching. Conclusions HI has relatively unique sonographic features. Therefore, 2D-ultrasound combined with 3D-ultrasound may be an effective method for the prenatal diagnosis of HI. Moreover, a novel pathogenic ABCA12 gene mutation may provide important clues for future research on the etiology of HI. However, the authors consider that additional studies are needed to provide more evidence for prenatal diagnosis.

Long Tunneled External Ventricular Drains with Shunt Valves: A Technical Note.

BACKGROUND: External ventricular drain (EVD) is a basic operation in neurosurgery. Due to the limitation of its safe duration, some patients need to receive multiple drainage operations. We describe the long tunneled EVD (LTEVD) with shunt valves that effectively avoid multiple operations as a technical note. METHODS: The difference is that the middle part of the drainage tube is connected by an externalized shunt valve. The drainage tube is buried under the skin and the outlet is in the abdomen. The technique and more details are described. RESULTS: The connection between the LTEVD and the shunt valve is simple and the required materials are easily accessible. Externalized valves allow the cerebrospinal fluid to be visualized and more controllable, making it easier for physicians to manage the cerebrospinal fluid. No drainage tube failure or secondary infection was observed. The indwelling time of the drainage tube was greatly extended. CONCLUSIONS: LTEVD is effective and simple. It allows visual control of drainage flow, prolonging catheter indwelling time and eliminating the need for multiple surgeries.

A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients.

BACKGROUND: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and its prevalence is increasing. As an emerging therapy with a promising efficacy, immunotherapy has been extensively applied in the treatment of solid tumors. In addition, chromatin regulators (CRs), as essential upstream regulators of epigenetics, play a significant role in tumorigenesis and cancer development. METHODS: CRs and immune checkpoint-related genes (ICRGs) were obtained from the previous top research. The Genome Cancer Atlas (TCGA) was utilized to acquire the mRNA expression and clinical information of patients with EC. Correlation analysis was utilized for screen CRs-related ICRGs (CRRICRGs). By Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, prognosis related CRRICRGs were screened out and risk model was constructed. The Kaplan-Meier curve was used to estimate the prognosis between high- and low-risk group. By comparing the IC50 value, the drugs sensitivity difference was explored. We obtained small molecule drugs for the treatment of UCEC patients based on CAMP dataset. RESULTS: We successfully constructed a 9 CRRICRs-based prognostic signature for patients with UCEC and found the riskscore was an independent prognostic factor. The results of functional analysis suggested that CRRICRGs may be involved in immune processes associated with cancer. Immune characteristics analysis provided further evidence that the CRRICRGs-based model was correlated with immune cells infiltration and immune checkpoint. Eight small molecule drugs that may be effective for the treatment of UCEC patients were screened. Effective drugs identified by drug sensitivity profiling in high- and low-risk groups. CONCLUSION: In summary, our study provided novel insights into the function of CRRICRGs in UCEC. We also developed a reliable prognostic panel for the survival of patients with UCEC.

Brain connectivity markers in advanced Parkinson's disease for predicting mild cognitive impairment.

OBJECTIVES: Mild cognitive impairment (MCI) is a well-defined non-motor manifestation and a harbinger of dementia in Parkinson's disease. This study is to investigate brain connectivity markers of MCI using diffusion tensor imaging and resting-state functional MRI, and help MCI diagnosis in PD patients. METHODS: We evaluated 131 advanced PD patients (disease duration > 5 years; 59 patients with MCI) and 48 healthy control subjects who underwent a diffusion-weighted and resting-state functional MRI scanning. The patients were randomly assigned to training (n = 100) and testing (n = 31) groups. According to the Brainnetome Atlas, ROI-based structural and functional connectivity analysis was employed to extract connectivity features. To identify features with significant discriminative power for patient classification, all features were put into an all-relevant feature selection procedure within cross-validation loops. RESULTS: Nine features were identified to be significantly relevant to patient classification. They showed significant differences between PD patients with and without MCI and positively correlated with the MoCA score. Five of them did not differ between general MCI subjects and healthy controls from the ADNI database, which suggested that they could uniquely play a part in the MCI diagnosis of PD. On basis of these relevant features, the random forest model constructed from the training group achieved an accuracy of 83.9% in the testing group, to discriminate patients with and without MCI. CONCLUSIONS: The results of our study provide preliminary evidence that structural and functional connectivity abnormalities may contribute to cognitive impairment and allow to predict the outcome of MCI diagnosis in PD. KEY POINTS: • Nine MCI markers were identified using an all-relevant feature selection procedure. • Five of nine markers differed between MCI and NC in PD, but not in general persons. • A random forest model achieved an accuracy of 83.9% for MCI diagnosis in PD.

Electrode Reconstruction Assists Postoperative Contact Selection in Deep Brain Stimulation.

BACKGROUND: Postoperative contact selection of deep brain stimulation (DBS), testing one contact at a time, is a clinically time-consuming procedure being challenged by incoming applications of more complex DBS leads. The objective of this study is to guide clinicians to select the optimal contact by neuroanatomic information derived from electrode reconstruction. METHODS: We reviewed 33 patients with Parkinson disease who underwent bilateral subthalamic nucleus (STN) DBS with preoperative magnetic resonance imaging and postoperative computed tomography scan. All electrodes were reconstructed in standardized Montreal Neurological Institute and Hospital space, and the volume of tissue activated (VTA) was estimated for each contact. According to the DISTAL atlas, we calculated 6 neuroanatomic parameters: the distances of each contact to the STN and the motor part of the STN (M-STN), the volumes of the overlapping areas of the VTA and STN/M-STN, and the number and ratio of fiber tracts through both the VTA and motor areas (primary motor cortex and supplementary motor area). RESULTS: All 6 parameters showed significant group differences between clinical optimal and nonoptimal contacts by permutation test. Moreover, the possibility of being the optimal contact was estimated for all contacts under the combination of these 6 parameters using a generalized linear model, which resulted in accuracy of 72.7% for prediction of contact selection. CONCLUSIONS: Electrode reconstruction could assist in selecting the clinical optimal contact and improving its efficiency.