Application of interpretable machine learning algorithms to predict distant metastasis in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

Morphological and Compositional Features of Chronic Internal Carotid Artery Occlusion in MR Vessel Wall Imaging Predict Successful Endovascular Recanalization.

Background: We sought to determine if the morphological and compositional features of chronic internal carotid artery occlusion (CICAO), as assessed by MR vessel wall imaging (MR-VWI), initially predict successful endovascular recanalization. Methods: Consecutive patients with CICAO scheduled for endovascular recanalization were recruited. MR-VWI was performed within 1 week prior to surgery for evaluating the following features: proximal stump morphology, extent of occlusion, occlusion with collapse, arterial tortuosity, the presence of hyperintense signals (HIS) and calcification in the occluded C1 segment. Multivariate logistic regression was used to identify features associated with technical success and construct a prediction model. Results: Eighty-three patients were recruited, of which fifty-seven (68.7%) were recanalized successfully. The morphological and compositional characteristics of CICAO were associated with successful recanalization, including occlusions limited to C1 and extensive HIS, as well as the absence of extensive calcification, absence of high tortuosity, and absence of artery collapse. The MR CICAO score that comprised the five predictors showed a high predictive ability (area under the curve: 0.888, p < 0.001). Conclusion: the MR-VWI characteristics of CICAO predicted the technical success of endovascular recanalization and may be leveraged for identifying patients with a high probability of successful recanalization.

Irregular Pulsation of Intracranial Aneurysm Detected by Four-Dimensional CT Angiography and Associated With Small Aneurysm Rupture: A Single-Center Prospective Analysis.

Objectives: Predicting the risk of rupture of small intracranial aneurysms remains challenging. The irregular pulsation of aneurysms detected by four-dimensional CT angiography (4D-CTA) could be an imaging marker of aneurysm vulnerability. We aimed to investigate the association of irregular pulsation with small aneurysm rupture. Materials and Methods: This was a prospective study on intracranial aneurysms detected by 4D-CTA from October 2017 to January 2020. A total of 242 consecutive patients with 316 aneurysms were enrolled. Irregular pulsation was defined as a temporary focal protuberance on more than 3 consecutive frames of the 20 phases in the RR interval. Small aneurysms were defined as those <7 mm. Univariate and multivariate analyses were performed to determine the independent predictors of small aneurysm rupture. Results: A total of 169 patients with 217 small intracranial aneurysms were included. Fourteen (6.5%) of the aneurysms had ruptured, and 77 (35.5%) had irregular pulsation. There were no significant differences in age, sex, hypertension, smoking, diabetes, drinking, or hyperlipidemia between the ruptured and unruptured aneurysm groups. The univariate analysis showed that smaller vessel size (p = 0.008), larger size ratio (p = 0.003), larger aspect ratio (p = 0.006), larger flow angle (p = 0.001), large vessel angle (p = 0.004), middle cerebral artery aneurysms (p = 0.046), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysm (p = 0.006), irregular aneurysm (p = 0.001), and t presence of irregular pulsation (p = 0.001) were associated with small aneurysm rupture. The multivariate analysis showed that the presence of irregular pulsation (p = 0.003), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysms (p = 0.014), and larger flow angle (p = 0.006) was independently associated with aneurysm rupture. Multivariate analysis of predictors of the irregular pulsation of small aneurysms showed that the aneurysm rupture (p = 0.022), irregular aneurysm (p < 0.001), and large size ratio (p = 0.005) were independently associated with the presence of irregular pulsation. Conclusions: The ruptured small aneurysms more often had irregular pulsation. The irregular pulsation was independently associated with aneurysm rupture and may help evaluate the risk of rupture of small intracranial aneurysms.

Touchless Sensing Interface Based on the Magneto-Piezoresistive Effect of Magnetic Microstructures with Stacked Conductive Coating.

Robotics capable of human-like operations need to have electronic skin (e-skin) with not only tactile sensing functions but also proximity perception abilities. Especially, under the current widespread of COVID-19 pandemic, touchless interfaces are highly desirable. Magnetoreception, with inherent specificity for magnetic objects, is an effective approach to construct a non-contact sensing e-skin. In this work, we propose a new touchless sensing mechanism based on the magneto-piezoresistive effect. The substrate of the sensor is made of hierarchically microstructured ferromagnetic polydimethylsiloxane, coated with a three-dimensional (3D) piezoresistive network. The 3D network is constructed by stacked layers of reduced graphene oxide and carbon nanotubes through layer-by-layer deposition. With this integrated design, a magnetic force induced on the ferromagnetic substrate can seamlessly be applied to the piezoresistive layer of the sensor. Because the magnetic force relates strongly to the approaching distance, the position information can be transduced into the resistance change of the piezoresistive network. The flexible proximity sensor exhibits an ultrahigh spatial resolution of 60 µm, a sensitivity of 50.47 cm-1, a wide working range of 6 cm, and a fast response of 10 ms. The repeatable performance of the sensor is shown by over 5000 cycles of approaching-separation test. We also demonstrate successful application of the sensor in 3D positioning and motion tracking settings, which is critical for touchless tactile perception-based human-machine interactions.

Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats.

AIMS: Nerve growth factor (NGF) has been reported to prevent neuronal damage and contributes to the functional recovery in animal brain injury models and human ischemic disease as well. We aimed to investigate a potential therapeutic effect of NGF gene treatment in ischemic stroke and to estimate the functional recovery both at the cellular and cognitive levels in an ischemia rat model. METHODS: After microinjection of pseudolentivirus-delivered ß-NGF into an established ischemic stroke model in rats (tMCAO), we estimated neuronal cell apoptosis with TUNEL labeling and neurogenesis by cell proliferation marker Ki67 staining in both ischemic core and penumbra of striatum. Furthermore, we used behavioral functional tests, Morris water maze performance, to evaluate cognitive functional recovery in vivo and propose a potential underlying mechanism. RESULTS: We found that pseudolentivirus-mediated delivery of ß-NGF gene into the brain induced high expression in striatum of the infarct core area after ischemia in rats. The ß-NGF overexpression in the striatal infarction core after ischemia not only improved neuronal survival by reducing cell apoptosis and increasing cell proliferation, but also rescued cognitive functional impairment through upregulation of GAP-43 protein expression in tMCAO rat model of ischemia. CONCLUSION: This study demonstrates a potential ß-NGF gene therapy by utilization of pseudolentivirus in ischemia and indicates future applications of NGF gene treatment in ischemic patients.

The Management for Intracranial Metastatic Neuroendocrine Tumor With Lung Origin.

Neuroendocrine tumor (NET) is not a common source of brain metastasis and the standard management of intracranial metastatic NET with lung origin remains unclear as a result of its rarity. We aimed to generalize some applicable protocols from our current 2 cases and relevant literature.

Silencing of Id2 attenuates hypoxia/ischemia-induced neuronal injury via inhibition of neuronal apoptosis.

Cerebral ischemic stroke has long been recognized as a prevalent and serious neurological disease that was associated with high mortality and morbidity. However, the current therapeutic protocols remain suboptimal with major mechanisms underlying stroke urgently warranted. Inhibitor of DNA binding/differentiation 2 (Id2) is found to be up-regulated in neuronal cells following hypoxia/ischemia (H/I). This study was aimed to investigate whether knockdown of Id2 in neuronal cells could protect them from hypoxic and ischemic injury both in vitro and in vivo. Flow cytometric analysis was employed to assess neuronal apoptosis in CoCl2-treated neuroblastoma B35 cells engineered to overexpress or knockdown Id2 expression. In vivo knockdown of Id2 was performed in Sprague-Dawley rats by a single intracerebroventricular injection of Cy3-labeled and cholesterol-modified Id2-siRNA. We found that knockdown of Id2 attenuated H/I-induced neuronal apoptosis in vitro while overexpression of Id2 produced an opposite effect. In a rat model of middle cerebral artery occlusion (MCAO), in vivo knockdown of Id2 significantly improved neurological deficits, reduced the volume of ischemic infarction and diminished the neuronal apoptosis in the penumbra area. Double immunofluorescence staining showed less co-localization of retinoblastoma tumor suppressor protein (Rb)-Id2 but greater co-localization of Rb-E2F1 in the penumbra area. Cell cycle assay further demonstrated that Id2 knockdown induced G0/G1 cell cycle arrest in CoCl2-treated B35 cells. The present data support the implication of Id2 in the modulation of H/I-induced neuronal apoptosis and may provide a potential therapeutic option to protect brain tissues from ischemic injury by inhibition of its expression.

ID1 affects the efficacy of radiotherapy in glioblastoma through inhibition of DNA repair pathways.

Glioblastoma multiforme (GBM) is characterized by poor therapeutic response and poor overall survival. It is crucial that more effective therapies be developed for the treatment of GBM. Inhibitor of DNA binding protein-1 (ID1) has been shown to maintain the self-renewal capacity of neural stem cells and might be involved in the therapeutic resistance of GBM. In the present study, we explored survival data from the The Cancer Genome Atalas database that were based on ID1 expression for patients diagnosed with primary GBMs. Interestingly, patients with high ID1 expression had better survival than patients with low ID1 expression, and a strong correlation was found between radiotherapy efficacy, ID1 expression, and overall survival. We further investigated the relationship between ID1 expression and the radiosensitivity of glioblastoma using glioblastoma cell lines. The clonogenic formation assay showed that U87 ID1-shRNA cells were much less sensitive to radiation. Moreover, both the results of the γH2AX foci staining assay and the comet assay further revealed that ID1 negatively regulates DNA repair processes by downregulating the expression of genes such as DNA ligase IV (LIG4) and ataxia-telangiectasia-mutated. Additionally, ID1 induces G2/M arrest in U87 cells. Taken together, these results suggest that ID1 may be a new prognostic marker for GBM and have important implications for the therapeutic strategies used to treat GBM patients.

Dynamic expression of cerebral cortex and hippocampal glutamate transporters in a rat model of chest compression-induced global cerebral ischemia.

The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and hippocampus. After 24 hours of ischemia, expression of glutamate transporter-1 significantly decreased in the cerebral cortex and hippocampus, which was accompanied by neuronal necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1 decreased in the hippocampal CA1 region and cortex, and was accompanied by apoptosis. Expression of glutamate-aspartate transporter remained unchanged at 6 hours-7 days after ischemia. These results suggested that glutamate transporter levels were altered at different periods of cerebral ischemia.

Endoscopic study for the pterygopalatine fossa anatomy: via the middle nasal meatus-sphenopalatine foramen approach.

OBJECTIVE: The purposes of this study were to locate the constant anatomic landmarks, which are very important and helpful for endoscopic surgery and not well described for the pterygopalatine fossa (PPF) surgery via the middle nasal meatus-sphenopalatine foramen approach to establish a safe surgical mode. METHODS: Eight cases of adult skull specimens were selected for the simulated surgery. The Messerklinger surgical approach was used under the endoscope. The uncinate process was removed successively, and the anterior ethmoid sinus and posterior ethmoid sinus were opened. The opening of the maxillary sinus was identified and was expanded forward and backward. The ethmoidal crest was found and was used as an anatomic landmark to find the sphenopalatine foramen. The sphenopalatine artery was protected and was used as a guide to enter the PPF region. The sphenopalatine artery was followed conversely to anatomize the blood vessels and nerves in the PPF. RESULTS: It was found that our surgical procedure provides a clear view of the constant anatomic landmark including ethmoidal crest and sphenopalatine foramen. By retrograde dissection, following the sphenopalatine artery, which runs out of the sphenopalatine foramen behind the ethmoidal crest, the internal maxillary artery (IMA) and the branches of the IMA in the PPF were exposed. Posterior to the sphenopalatine artery, the typical Y-shaped structure with the pterygopalatine ganglion as the center was visible when the IMA and its branches were moved downward and outward. The Y structure, which is consisted of the pterygopalatine ganglion, branches of the internal maxillary nerve, vidian nerve, and descending palatine nerve, served as the other anatomic landmark. By following the Y structure, it was easy to locate the pterygoid canal, foramen rotundum, and the infraorbital nerve, and the integrity of the nerve structure could be protected. CONCLUSION: Endoscopic PPF surgery via the middle nasal meatus-sphenopalatine foramen approach is safe, and the ethmoidal crest, sphenopalatine foramen, and Y structure with the pterygopalatine ganglion in the center are important anatomic landmarks that can be referred to during the surgery.

[The effect of simvastatin on the regeneration of sciatic nerve with crush injury in rats].

AIM: To explore the effect of Simvastatin on the regeneration of sciatic nerve with crush injury in rats. METHODS: Animals were randomized into the following experimental groups: Simvastatin-treated, vehicle and sham-operated groups. Sciatic nerves with crush injury were performed. After surgery, the functional evaluation of nerve recovery, electrophysiologic assessment, histological assessment, serum IL-6 and lipid were performed. RESULTS: The toe spread index of Simvastatin-treated rats after operation was higher significantly than vehicle rats at 5 d and 8 d (P<0.05). CMAP was higher and NCV was faster (P < 0.05). The serum IL-6 at 5 d of post-operation was significant lower (P < 0.05). Total serum cholesterol of Simvastatin-treated animals was higher than that of other animals (P < 0.05) at 2 weeks of post-operation. The histological analysis showed that the numbers of myelinated axons and the thickness of myelin sheath of Simvastatin-treated crush injury animals at 4 weeks of post-operation were more than that of vehicle animals. CONCLUSION: The present study showed that Simvastatin could promote the regeneration of the sciatic nerve after crush injury in rats, partly through inhibiting immune and inflammatory responses and making the balance of serum cholesterol during these processes.