Whole-cycle management of women with epilepsy of child-bearing age: ontology construction and application.

BACKGROUND: The effective management of epilepsy in women of child-bearing age necessitates a concerted effort from multidisciplinary teams. Nevertheless, there exists an inadequacy in the seamless exchange of knowledge among healthcare providers within this context. Consequently, it is imperative to enhance the availability of informatics resources and the development of decision support tools to address this issue comprehensively. MATERIALS AND METHODS: The development of the Women with Epilepsy of Child-Bearing Age Ontology (WWECA) adhered to established ontology construction principles. The ontology's scope and universal terminology were initially established by the development team and subsequently subjected to external evaluation through a rapid Delphi consensus exercise involving domain experts. Additional entities and attribute annotation data were sourced from authoritative guideline documents and specialized terminology databases within the respective field. Furthermore, the ontology has played a pivotal role in steering the creation of an online question-and-answer system, which is actively employed and assessed by a diverse group of multidisciplinary healthcare providers. RESULTS: WWECA successfully integrated a total of 609 entities encompassing various facets related to the diagnosis and medication for women of child-bearing age afflicted with epilepsy. The ontology exhibited a maximum depth of 8 within its hierarchical structure. Each of these entities featured three fundamental attributes, namely Chinese labels, definitions, and synonyms. The evaluation of WWECA involved 35 experts from 10 different hospitals across China, resulting in a favorable consensus among the experts. Furthermore, the ontology-driven online question and answer system underwent evaluation by a panel of 10 experts, including neurologists, obstetricians, and gynecologists. This evaluation yielded an average rating of 4.2, signifying a positive reception and endorsement of the system's utility and effectiveness. CONCLUSIONS: Our ontology and the associated online question and answer system hold the potential to serve as a scalable assistant for healthcare providers engaged in the management of women with epilepsy (WWE). In the future, this developmental framework has the potential for broader application in the context of long-term management of more intricate chronic health conditions.

Adaptive Dosage Strategy of Levetiracetam in Chinese Epileptic Patients: Focus on Pregnant Women.

There is presently no efficient dose individualization strategy for the use of antiseizure medications in epileptic pregnant patients. This study aimed to develop a population pharmacokinetics model for levetiracetam and propose a tailored adaptive individualized dosage strategy for epileptic pregnant patients. A total of 322 levetiracetam plasma concentrations from 238 patients with epilepsy were included, including 216 women with epilepsy (20.83% of whom were pregnant). The levetiracetam plasma concentration was measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were modeled using a nonlinear mixed-effects model. The resultant model served as the basis for simulating the dosage adjustment strategy. A one-compartment model with first-order elimination best described the pharmacokinetic data of levetiracetam. The apparent clearance (CL/F) was 3.43 L/h (95% CI 3.30-3.56) and the apparent volume of distribution was 43.7 L (95% CI 40.4-47.0) for a typical individual of 57.2 kg. Pregnancy and body weight were found to be significant covariates of CL/F of levetiracetam. The recommended regimen of levetiracetam could be predicted by the population pharmacokinetic model based on body weight, gestational age, and the daily dose of levetiracetam taken before pregnancy.

China's energy-water-land system co-evolution under carbon neutrality goal and climate impacts.

China's 2060 carbon neutrality goal has significant implications for energy, water, and land systems. However, the multi-sector dynamics among China's energy-water-land system have rarely been examined explicitly. This study adopts an integrated assessment framework to simulate China's energy-water-land system co-evolution under alternative carbon neutrality scenarios and climate impacts. Results show that although the net zero emission target provides the incentive for the energy system to move away from fossil fuels, total water withdrawal will increase due to the deployment of nuclear, bioenergy, and coal power plants with carbon capture and storage. Diversifying the negative emission technologies, by leveraging direct air capture technology, can alleviate the potential water stress and land use conflicts, which would otherwise be exacerbated by large-scale deployment of afforestation and bioenergy with carbon capture and storage. Northwest and northeast regions of China are the hotspots experiencing water withdrawal increases, while Bohai Rim and coastal regions are identified to experience fierce land competition. This study demonstrates the potential for general applicability to carry out resource planning and policy evaluation from the multi-sector coordination perspective.

Quantitation of levetiracetam concentrations in plasma and saliva samples by ultra-performance liquid chromatography-tandem mass spectrometry: Application to therapeutic drug monitoring for pregnant women with epilepsy.

Although levetiracetam (LEV) has favorable linear pharmacokinetic properties, therapeutic drug monitoring (TDM) is necessary for pregnant women with epilepsy. This study aims to build a simple, reliable, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining LEV concentrations in plasma and saliva samples, to support the routine TDM of LEV in Chinese pregnant women with epilepsy. The stable isotope-labeled LEV-d6 was used as the internal standard. The extracted samples were analyzed using a UPLC-MS/MS system with positive electrospray ionization. Mobile phase A was water containing 5 mM ammonium acetate and 0.1% formic acid, and phase B was 1:1 methanol-acetonitrile with 0.1% formic acid. The method was validated and utilized to determine LEV concentrations in non-pregnant and pregnant patients with epilepsy. The developed method was validated in both plasma and saliva samples over a concentration range of 0.1-50 µg/mL. The intra- and inter-batch accuracy for LEV ranged from -7.0% to 2.9%, with precisions between 2.7% and 9.3%. In pregnant patients, the mean dose-standardized LEV trough plasma concentrations were significantly lower than those in non-pregnant patients (4.73 ± 2.99 vs. 7.74 ± 3.59 ng/mL per mg/day; P < 0.0001). It is recommended that the TDM of LEV should be routinely performed during the different stages of pregnancy.

A disulfiram derivative against lung cancer via the Notch signaling pathway without neurotoxicity and hepatotoxicity.

The exploration of novel anti-lung cancer small-molecule drugs is important for drug resistance and adverse effects of chemotherapeutic drugs in current clinics. Disulfiram (DSF), as an antidote, has been proven to have excellent antitumor effects in combination with copper (Cu). However, the risk for potential neurotoxicity and hepatotoxicity in clinical use, as well as its poor water solubility, limits its use. In this study, we identified a DSF derivative, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine, which could greatly increase the water solubility by converting it to a calcium salt (DS-NAC). The anti-lung cancer pharmacodynamic studies in vitro of DS-NAC were evaluated and a mouse model of lung cancer in situ was established to explore the therapeutic effects of DS-NAC compared with DSF and oxaliplatin (OXA). The results demonstrated that DS-NAC combined with Cu had superior cytotoxicity to DSF and OXA in the CCK8 assay against lung cancer cells, and exhibited potent anti-metastatic, epithelial-mesenchymal transition inhibition. In addition, DS-NAC showed better antitumor effects than DSF and comparable effects to OXA in lung cancer in situ model. In terms of the antitumor mechanism, we discovered that DS-NAC in combination with Cu exerted a greater inhibitory effect on the Notch pathway than DSF, which may account for its excellent antitumor effects. Finally, we verified the safety of DS-NAC in vivo, showing lower hepatotoxicity and neurotoxicity compared with DSF and OXA. DS-NAC is a promising anti-lung cancer drug with a favorable safety profile.

Modulation of protein-DNA binding reveals mechanisms of spatiotemporal gene control in early Drosophila embryos.

It is well known that enhancers regulate the spatiotemporal expression of their target genes by recruiting transcription factors (TFs) to the cognate binding sites in the region. However, the role of multiple binding sites for the same TFs and their specific spatial arrangement in determining the overall competency of the enhancer has yet to be fully understood. In this study, we utilized the MS2-MCP live imaging technique to quantitatively analyze the regulatory logic of the snail distal enhancer in early Drosophila embryos. Through systematic modulation of Dorsal and Twist binding motifs in this enhancer, we found that a mutation in any one of these binding sites causes a drastic reduction in transcriptional amplitude, resulting in a reduction in mRNA production of the target gene. We provide evidence of synergy, such that multiple binding sites with moderate affinities cooperatively recruit more TFs to drive stronger transcriptional activity than a single site. Moreover, a Hidden Markov-based stochastic model of transcription reveals that embryos with mutated binding sites have a higher probability of returning to the inactive promoter state. We propose that TF-DNA binding regulates spatial and temporal gene expression and drives robust pattern formation by modulating transcriptional kinetics and tuning bursting rates.

IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children.

Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12-1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P < .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P > .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P > .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.

Antinuclear Antibodies in Erythema Multiforme: Transient Occurrence During Acute Illness.

BACKGROUND: Children with target lesions are frequently diagnosed with erythema multiforme (EM). EM was not previously thought to be associated with any specific autoimmune serological abnormality. METHODS: We report the case of a 7-year-old girl who developed rashes all over her body with target shaped lesions. Based on clinical appearance and medical history, she was diagnosed with severe erythema multiforme and treated with methylprednisolone. Relevant laboratory tests were performed at admission. RESULTS: At the height of her infection, the antinuclear antibody (ANA) test showed a positive ANA with a titer of 1:100 (speckled pattern) and positive anti-SSA and anti-Ro-52 antibodies. Then she was adjusted for medication. After a week, the infection was relieved, and the re-examination was negative for ANA, anti-SSA, and anti-Ro-52 antibodies. CONCLUSIONS: In previously reported EM cases, ANA is generally not considered to be present. The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of EM infection. Its correlation with infection severity warrants further research on the mechanism of autoantibody formation in EM.

A Two-Stage Voting-Boosting Technique for Ensemble Learning in Social Network Sentiment Classification.

In recent years, social network sentiment classification has been extensively researched and applied in various fields, such as opinion monitoring, market analysis, and commodity feedback. The ensemble approach has achieved remarkable results in sentiment classification tasks due to its superior performance. The primary reason behind the success of ensemble methods is the enhanced diversity of the base classifiers. The boosting method employs a sequential ensemble structure to construct diverse data while also utilizing erroneous data by assigning higher weights to misclassified samples in the next training round. However, this method tends to use a sequential ensemble structure, resulting in a long computation time. Conversely, the voting method employs a concurrent ensemble structure to reduce computation time but neglects the utilization of erroneous data. To address this issue, this study combines the advantages of voting and boosting methods and proposes a new two-stage voting boosting (2SVB) concurrent ensemble learning method for social network sentiment classification. This novel method not only establishes a concurrent ensemble framework to decrease computation time but also optimizes the utilization of erroneous data and enhances ensemble performance. To optimize the utilization of erroneous data, a two-stage training approach is implemented. Stage-1 training is performed on the datasets by employing a 3-fold cross-segmentation approach. Stage-2 training is carried out on datasets that have been augmented with the erroneous data predicted by stage 1. To augment the diversity of base classifiers, the training stage employs five pre-trained deep learning (PDL) models with heterogeneous pre-training frameworks as base classifiers. To reduce the computation time, a two-stage concurrent ensemble framework was established. The experimental results demonstrate that the proposed method achieves an F1 score of 0.8942 on the coronavirus tweet sentiment dataset, surpassing other comparable ensemble methods.

Lead poisoning in a 6-month-old infant: a case report.

Background: Lead is a toxic element of the environment that leads to major complications once it enters the blood stream, affecting multiple organs and systems of the body. Methods: We present a case of a 6-month-old female infant diagnosed with lead poisoning after presenting for routine child health care. The child's mother denied that the infant had a history of exposure to lead-containing substances. After a month of calcium supplementation, the patient's blood lead level remained elevated. We then tested the blood lead level of the mother and father. The results showed that the blood lead level of the mother was 77.0 µg/L and that of the father was 36.9 µg/L. The high blood lead level of the mother attracted our attention. We found that the mother had been using an external traditional Chinese medicine, Hu Wang Fen, which contains lead. After the mother's discontinuation of use of the traditional medicine, the child was treated with symptomatic treatment and chelation therapy. Subsequently, the patient's blood lead level decreased significantly. Results: Lead toxicity can be a life-threatening problem because of its potential for severe complications. In children, there is no safe blood lead level, and the toxic effects of lead can be prevented by the awareness and avoidance of traditional Chinese medicines that may contain lead. Conclusion: Even though the diagnosis of lead poisoning remains difficult in children, it must be taken into consideration by the clinician when treating a child using traditional Chinese medicines.

Targeting adverse effects of antiseizure medication on offspring: current evidence and new strategies for safety.

INTRODUCTION: For women with epilepsy of reproductive age, antiseizure medications (ASMs) are associated with an increased risk of offspring malformations. There are safety concerns for most anti-seizure medications in the perinatal period, and there is a clear need to identify safe medications. ASMs must transport through biological barriers to exert toxic effects on the fetus, and transporters play essential roles in trans-barrier drug transport. Therefore, it is vital to understand the distribution and properties of ASM-related transporters in biological barriers. AREAS COVERED: This study reviews the structure, transporter distribution, and properties of the blood-brain, placental, and blood-milk barrier, and summarizes the existing evidence for the trans-barrier transport mechanism of ASMs and standard experimental models of biological barriers. EXPERT OPINION: Ideal ASMs in the perinatal period should have the following characteristics: 1) Increased transport through the blood-brain barrier, and 2) Reduced transport of the placental and blood-milk barriers. Thus, only low-dose or almost no antiseizure medication could enter the fetus's body, which could decrease medication-induced fetal abnormalities. Based on the stimulated structure and molecular docking, we propose a development strategy for new ASMs targeting transporters of biological barriers to improve the perinatal treatment of female patients with epilepsy.

BRD4 is involved in viral exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Our previous studies have suggested that bromodomain protein 4 (BRD4) is increased in the lung of stable chronic obstructive pulmonary disease (COPD) patients, which has been shown to be involved in inflammatory responses. We investigated its role in the viral exacerbation of COPD. METHODS: BRD4, interleukin (IL)-6 and IL-8 were measured in the blood and sputum of stable COPD patients and patients with viral exacerbation. Mice were exposed to cigarette smoke (CS) and/or infected with influenza virus as an in vivo model. BRD4, IL-6 and keratinocyte-derived chemokine (KC) were measured in the lung. BEAS-2B cells were treated with CS extract and/or influenza virus as an in vitro model. BRD4, IL-6 and IL-8 were measured in the cells and/or culture supernatant. RESULTS: BRD4 was increased in COPD patients with viral exacerbation compared with those in stable condition and its expression was correlated with IL-6 and IL-8 expression. Inflammatory cells, IL-6, KC and BRD4 were synergistically induced in the lung of mice by viral infection and CS exposure, and the former three were decreased by JQ1 (BRD4 inhibitor) treatment. IL-6, IL-8 and BRD4 were significantly induced by CS extract and influenza virus in bronchial epithelial cells, and this upregulation was suppressed by knockdown of BRD4 expression. CONCLUSIONS: Our findings indicate that CS and viruses may synergistically induce IL-6 and IL-8 expression through their synergistic induction of BRD4 expression, which might contribute to the enhanced inflammatory response in the viral exacerbation of COPD.

Racial differences in time to blood pressure control of aneurysmal subarachnoid hemorrhage patients: A single-institution study.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage occurs in approximately 30,000 patients annually in the United States. Uncontrolled blood pressure is a major risk factor for aneurysmal subarachnoid hemorrhage. Clinical guidelines recommend maintaining blood pressure control until definitive aneurysm securement occurs. It is unknown whether racial differences exist regarding blood pressure control and outcomes (HLOS, discharge disposition) in aneurysmal subarachnoid hemorrhage. Here, we aim to assess whether racial differences exist in 1) presentation, 2) clinical course, and 3) outcomes, including time to blood pressure stabilization, for aSAH patients at a large tertiary care medical center. METHODS: We conducted a retrospective review of adult aneurysmal subarachnoid hemorrhage cases from 2013 to 2019 at a single large tertiary medical center. Data extracted from the medical record included sex, age, race, insurance status, aneurysm location, aneurysm treatment, initial systolic and diastolic blood pressure, Hunt Hess grade, modified Fisher score, time to blood pressure control (defined as time in minutes from first blood pressure measurement to the first of three consecutive systolic blood pressure measurements under 140mmHg), hospital length of stay, and final discharge disposition. RESULTS: 194 patients met inclusion criteria; 140 (72%) White and 54 (28%) Black. While White patients were more likely than Black patients to be privately insured (62.1% versus 33.3%, p < 0.001), Black patients were more likely than White patients to have Medicaid (55.6% versus 15.0%, p < 0.001). Compared to White patients, Black patients presented with a higher median systolic (165 mmHg versus 148 mmHg, p = 0.004) and diastolic (93 mmHg versus 84 mmHg, p = 0.02) blood pressure. Black patients had a longer median time to blood pressure control than White patients (200 minutes versus 90 minutes, p = 0.001). Black patients had a shorter median hospital length of stay than White patients (15 days versus 18 days, p < 0.031). There was a small but statistically significant difference in modified Fisher score between black and white patients (3.48 versus 3.17, p = 0.04).There were no significant racial differences present in sex, Hunt Hess grade, discharge disposition, complications, or need for further interventions. CONCLUSION: Black race was associated with higher blood pressure at presentation, longer time to blood pressure control, but shorter hospital length of stay. No racial differences were present in aneurysmal subarachnoid hemorrhage associated complications or interventions.

A pilot study on identifying gene signatures as markers for predicting patient response to antiseizure medications.

The majority of the biomarkers were associated with the diagnosis of epilepsy and few of them can be applied to predict the response to antiseizure medications (ASMs). In this study, we identified 26 significantly up-regulated genes and 32 down-regulated genes by comparing the gene expression profiles of patients with epilepsy that responded to valproate with those without applying any ASM. The results of gene set enrichment analysis indicated that the ferroptosis pathway was significantly impacted (p = 0.0087) in patients who responded to valproate. Interestingly, the gene NCOA4 in this pathway exhibited significantly different expression levels between the two groups, indicating that NCOA4 could serve as a potential biomarker to better understand the mechanism of valproate resistance. In addition, six up-regulated genes SF3A2, HMGN2, PABPN1, SSBP3, EFTUD2, and CREB3L2 as well as six down-regulated genes ZFP36L1, ACRC, SUB1, CALM2, TLK1, and STX2 also showed significantly different expression patterns between the two groups. Moreover, based on the gene expression profiles of the patients with the treatment of valproate, carbamazepine, and phenytoin, we proposed a strategy for predicting the response to the ASMs by using the Connectivity Map scoring method. Our findings could be helpful for better understanding the mechanisms of drug resistance of ASMs and improving the clinical treatment of epilepsy.

Modulation of protein-DNA binding reveals mechanisms of spatiotemporal gene control in early Drosophila embryos.

It is well known that enhancers regulate the spatiotemporal expression of their target genes by recruiting transcription factors (TFs) to the cognate binding sites in the region. However, the role of multiple binding sites for the same TFs and their specific spatial arrangement in determining the overall competency of the enhancer has yet to be fully understood. In this study, we utilized the MS2-MCP live imaging technique to quantitatively analyze the regulatory logic of the snail distal enhancer in early Drosophila embryos. Through systematic modulation of Dorsal and Twist binding motifs in this enhancer, we found that a mutation in any one of these binding sites causes a drastic reduction in transcriptional amplitude, resulting in a reduction in total mRNA production of the target gene. We provide evidence of synergy, such that multiple binding sites with moderate affinities cooperatively recruit more TFs to drive stronger transcriptional activity than a single site. Moreover, a Hidden Markov-based stochastic model of transcription reveals that embryos with mutated binding sites have a higher probability of returning to the inactive promoter state. We propose that TF-DNA binding regulates spatial and temporal gene expression and drives robust pattern formation by modulating transcriptional kinetics and tuning bursting rates.

Increased CAP37 Expression in Stable Chronic Obstructive Pulmonary Disease.

OBJECTIVE: Cationic antimicrobial protein of 37 kDa (CAP37), a neutrophil-derived protein originally identified for its antimicrobial activity, is now known to have many regulatory effects on host cells. However, its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) has not been studied. We therefore investigated the expression of CAP37 in COPD and its effects on airway structural cells, including bronchial epithelial cells, smooth muscle cells, and fibroblasts. METHODS: CAP37 was detected in the lung tissue, sputum, and plasma of COPD patients and the control subjects, as well as in the neutrophils stimulated by cigarette smoke extract (CSE). BEAS-2B cells, human bronchial smooth muscle cells (HBSMCs), and MRC-5 cells were treated with CAP37 or an anti-CAP37 antibody plus CAP37. Interleukin (IL)-6 and IL-8 were detected in the BEAS-2B cells. The cell proliferation was analyzed in the HBSMCs. Collagens were also detected in the MRC-5 cells. RESULTS: The expression of CAP37 was increased in the lung tissue and sputum supernatant of the COPD patients compared with the control subjects. The sputum supernatant CAP37 levels were inversely correlated with the forced expiratory volume in the first second percentage predicted in COPD. CAP37 was induced by CSE stimulation in the peripheral blood neutrophils from healthy non-smokers. CAP37 induced expression of IL-6 and IL-8 in BEAS-2B cells, and collagen expression of lung fibroblasts (MRC-5 cells). However, CAP37 did not significantly alter the proliferation of the HBSMCs. CONCLUSION: Our findings indicated that neutrophil-derived CAP37 may be involved in airway inflammation and fibrosis in COPD via affecting the bronchial epithelial cells, and fibroblasts, thus suggesting a possible role of CAP37 in the development and progression of COPD.

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Signal transducer and activator of transcription 5 (STAT5) can be involved in the processes such as cell proliferation, differentiation, apoptosis, and hematopoiesis, and its dysregulation is closely associated with the development and progression of malignant tumors including leukemia and may affect the treatment outcome and prognosis of pediatric patients. Identification of STAT5 can facilitate targeted therapy to improve the response rate of children with acute lymphoblastic leukemia. This article reviews the impact of STAT5 on the development/progression, targeted therapy strategies and the prognosis of childhood acute lymphoblastic leukemia.

Functional Outcomes and Postoperative Cerebral Venous Sinus Thrombosis after Translabyrinthine Approach for Vestibular Schwannoma Resection: A Radiographic Demonstration of Anatomic Predictors.

Introduction While regarded as an effective surgical approach to vestibular schwannoma (VS) resection, the translabyrinthine (TL) approach is not without complications. It has been postulated that postoperative cerebral venous sinus thrombosis (pCVST) may occur as a result of injury and manipulation during surgery. Our objective was to identify radiologic, surgical, and patient-specific risk factors that may be associated with pCVST. Methods The Institutional Review Board (IRB) approval was obtained and the medical records of adult patients with VS who underwent TL craniectomy at University Hospitals Cleveland Medical Center between 2009 and 2019 were reviewed. Demographic data, radiographic measurements, and tumor characteristics were collected. Outcomes assessed included pCVST and the modified Rankin score (mRS). Results Sixty-one patients ultimately met inclusion criteria for the study. Ten patients demonstrated radiographic evidence of thrombus. Patients who developed pCVST demonstrated shorter internal auditory canal (IAC) to sinus distance (mean: 22.5 vs. 25.0 mm, p = 0.044) and significantly smaller petrous angles (mean: 26.3 vs. 32.7 degrees, p = 0.0045). Patients with good mRS scores (<3) appeared also to have higher mean petrous angles (32.5 vs. 26.8, p = 0.016). Koos' grading and tumor size, in our study, were not associated with thrombosis. Conclusion More acute petrous angle and shorter IAC to sinus distance are objective anatomic variables associated with pCVST in TL surgical approaches.

Structure-Activity Relationship (SAR) Model for Predicting Teratogenic Risk of Antiseizure Medications in Pregnancy by Using Support Vector Machine.

Teratogenicity is one of the main concerns in clinical medications of pregnant women. Prescription of antiseizure medications (ASMs) in women with epilepsy during pregnancy may cause teratogenic effects on the fetus. Although large scale epilepsy pregnancy registries played an important role in evaluating the teratogenic risk of ASMs, for most ASMs, especially the newly approved ones, the potential teratogenic risk cannot be effectively assessed due to the lack of evidence. In this study, the analyses are performed on any medication, with a focus on ASMs. We curated a list containing the drugs with potential teratogenicity based on the US Food and Drug Administration (FDA)-approved drug labeling, and established a support vector machine (SVM) model for detecting drugs with high teratogenic risk. The model was validated by using the post-marketing surveillance data from US FDA Spontaneous Adverse Events Reporting System (FAERS) and applied to the prediction of potential teratogenic risk of ASMs. Our results showed that our proposed model outperformed the state-of-art approaches, including logistic regression (LR), random forest (RF) and extreme gradient boosting (XGBoost), when detecting the high teratogenic risk of drugs (MCC and recall rate were 0.312 and 0.851, respectively). Among 196 drugs with teratogenic potential reported by FAERS, 136 (69.4%) drugs were correctly predicted. For the eight commonly used ASMs, 4 of them were predicted as high teratogenic risk drugs, including topiramate, phenobarbital, valproate and phenytoin (predicted probabilities of teratogenic risk were 0.69, 0.60 0.59, and 0.56, respectively), which were consistent with the statement in FDA-approved drug labeling and the high reported prevalence of teratogenicity in epilepsy pregnancy registries. In addition, the structural alerts in ASMs that related to the genotoxic carcinogenicity and mutagenicity, idiosyncratic adverse reaction, potential electrophilic agents and endocrine disruption were identified and discussed. Our findings can be a good complementary for the teratogenic risk assessment in drug development and facilitate the determination of pharmacological therapies during pregnancy.

Bypassing the intensive care unit for patients with acute ischemic stroke secondary to large-vessel occlusion.

OBJECTIVE: Endovascular mechanical thrombectomy is safe and effective for the treatment of acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). Still, despite high rates of procedural success, it is routine practice to uniformly admit postthrombectomy patients to an intensive care unit (ICU) for postoperative observation. Predictors of ICU criteria and care requirements in the postmechanical thrombectomy ischemic stroke patient population are lacking. The goal of the present study is to identify risk factors associated with requiring ICU-level intervention following mechanical thrombectomy. METHODS: The authors retrospectively analyzed data from 245 patients undergoing thrombectomy for AIS from anterior circulation LVO at a comprehensive stroke and tertiary care center from January 2015 to March 2020. Clinical variables that predicted the need for critical care intervention were identified and compared. The performance of a binary classification test constructed from these predictive variables was also evaluated using a validation cohort. RESULTS: Seventy-six patients (31%) required critical care interventions. A recanalization grade lower than modified Thrombolysis in Cerebral Infarction (mTICI) scale grade 2B (odds ratio [OR] 3.625, p = 0.001), Alberta Stroke Program Early Computed Tomography Score (ASPECTS) < 8 (OR 3.643, p < 0.001), and presence of hyperdensity on postprocedure cone-beam CT (OR 2.485, p = 0.005) were significantly associated with the need for postthrombectomy critical care intervention. When applied to a validation cohort, a clearance classification scheme using these three variables demonstrated high positive predictive value (0.88). CONCLUSIONS: A recanalization grade lower than mTICI 2B, ASPECTS < 8, and postprocedure hyperdensity on cone-beam CT were shown to be independent predictors of requiring ICU-level care. Routine admission to ICU-level care can be costly and confer increased risk for hospital-acquired conditions. Safely and reliably identifying low-risk patients has the potential for cost savings, value-based care, and decreasing hospital-acquired conditions.