DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.

RNA helicase DHX9 is essential for genome stability by resolving aberrant R-loops. However, its regulatory mechanisms remain unclear. Here we show that SUMOylation at lysine 120 (K120) is crucial for DHX9 function. Preventing SUMOylation at K120 leads to R-loop dysregulation, increased DNA damage, and cell death. Cells expressing DHX9 K120R mutant which cannot be SUMOylated are more sensitive to genotoxic agents and this sensitivity is mitigated by RNase H overexpression. Unlike the mutant, wild-type DHX9 interacts with R-loop-associated proteins such as PARP1 and DDX21 via SUMO-interacting motifs. Fusion of SUMO2 to the DHX9 K120R mutant enhances its association with these proteins, reduces R-loop accumulation, and alleviates survival defects of DHX9 K120R. Our findings highlight the critical role of DHX9 SUMOylation in maintaining genome stability by regulating protein interactions necessary for R-loop balance.

Endometriosis, pregnancy and delivery complications: Evidence from the US nationwide inpatient sample 2005-2018.

OBJECTIVE: Endometriosis is associated with higher risk of ectopic pregnancy, premature delivery, miscarriage, and other adverse maternal and fetal complications. This study aimed to assess the impact of endometriosis on maternal and fetal outcomes of singleton pregnancies in a large nationally representative database. MATERIALS AND METHODS: This population-based, retrospective observational study extracted the data of women aged 20-49 years with singleton, spontaneously conceived pregnancies from the US Nationwide Inpatient Sample (NIS) database from 2005 to 2018. Included subjects were divided into those with ICD codes for endometriosis and those without (non-endometriosis group). Data of maternal and fetal outcomes were compared between groups and analyzed using regression analysis. RESULTS: After excluding 17,124 women who conceived with assisted reproductive technology (ART), 162,155 women with multiple pregnancies, and 27,847 with abnormal trend weight values (TRENDWT), a total of 8,584,269 women were eligible. After propensity score matching (PMS) case-control 1:4 by age, 45,560 remained (9112 (0.1%) with endometriosis, 36,448 without) and were included in the analysis. The mean age of women before matching was 28.7 years, and 30.5 years after matching. The most common comorbidity was chronic pulmonary disease (3.6%). Smoking frequency was higher in women with endometriosis compared to those without (4.8% vs. 2.4%). Multivariable analysis adjusted for confounders revealed that endometriosis was associated with significantly higher risk of maternal complications, including pre-eclampsia and eclampsia, antepartum hemorrhage, placenta previa, Cesarean delivery, post-partum hemorrhage, disseminated intravascular coagulation (DIC), transfusion, hemoperitoneum, and hospital stays ≥6 days. For fetal outcomes, endometriosis was associated with higher risk of intrauterine growth restriction (IUGR), premature birth, birth defects and abortion. CONCLUSION: Endometriosis during pregnancy is associated with maternal and fetal complications. Study findings may serve as a benchmark for expanding medical assistance for endometriosis-affected pregnant women.

Exploring the Potential Performance of Fibroscan for Predicting and Evaluating Metabolic Syndrome using a Feature Selected Strategy of Machine Learning.

Metabolic syndrome (MetS) includes several conditions that can increase an individual's predisposition to high-risk cardiovascular events, morbidity, and mortality. Non-alcoholic fatty liver disease (NAFLD) is a predominant cause of cirrhosis, which is a global indicator of liver transplantation and is considered the hepatic manifestation of MetS. FibroScan® provides an accurate and non-invasive method for assessing liver steatosis and fibrosis in patients with NAFLD, via a controlled attenuation parameter (CAP) and liver stiffness measurement (LSM or E) scores and has been widely used in current clinical practice. Several machine learning (ML) models with a recursive feature elimination (RFE) algorithm were applied to evaluate the importance of the CAP score. Analysis by ANOVA revealed that five symptoms at different CAP and E score levels were significant. All eight ML models had accuracy scores > 0.9, while treebags and random forest had the best kappa values (0.6439 and 0.6533, respectively). The CAP score was the most important variable in the seven ML models. Machine learning models with RFE demonstrated that using the CAP score to identify patients with MetS may be feasible. Thus, a combination of CAP scores and other significant biomarkers could be used for early detection in predicting MetS.

Intraoperative EMG recovery patterns and outcomes after RLN traction-related amplitude decrease during monitored thyroidectomy.

Objectives: Traction injury is the most common type of recurrent laryngeal nerve (RLN) injury in thyroid surgery. Intraoperative neuromonitoring (IONM) facilitates early detection of adverse electromyography (EMG) effect, and this corrective maneuver can reduce severe and repeated nerve injury. This study aimed to evaluate intraoperative patterns and outcomes of EMG decrease and recovery by traction injury. Methods: 644 patients received nerve monitored thyroidectomy with 1142 RLNs at risk were enrolled. Intermittent IONM with stimulating dissecting instrument (real-time during surgical procedure) and trans-thyroid cartilage EMG recording method (without electrode malpositioning issue) were used for nerve stimulation and signal recording. When an EMG amplitude showed a decrease of >50% during RLN dissection, the surgical maneuver was paused immediately. Nerve dissection was restarted when the EMG amplitude was stable. Results: 44/1142 (3.9%) RLNs exhibited a >50% EMG amplitude decrease during RLN dissection and all (100%) showed gradual progressive amplitude recovery within a few minutes after releasing thyroid traction (10 recovered from LOS; 34 recovered from a 51-90% amplitude decrease). Three EMG recovery patterns were noted, A-complete EMG recovery (n=14, 32%); B-incomplete EMG recovery with an injury point (n=16, 36%); C-incomplete EMG recovery without an injury point (n=14, 32%). Patients with postoperative weak or fixed vocal cord mobility in A, B, and C were 0(0%), 7(44%), and 2(14%), respectively. Complete EMG recovery was found in 14 nerves, and incomplete recovery was found in another 30 nerves. Temporary vocal cord palsy was found in 6 nerves due to unavoidable repeated traction. Conclusion: Early detection of traction-related RLN amplitude decrease allows monitoring of intraoperative EMG signal recovery during thyroid surgery. Different recovery patterns show different vocal cord function outcomes. To elucidate the recovery patterns can assist surgeons in the intraoperative decision making and postoperative management.