Identifying gray matter alterations in Cushing's disease using machine learning: An interpretable approach.

BACKGROUND: Cushing's Disease (CD) is a rare clinical syndrome characterized by excessive secretion of adrenocorticotrophic hormone, leading to significant functional and structural brain alterations as observed in Magnetic Resonance Imaging (MRI). While traditional statistical analysis has been widely employed to investigate these MRI changes in CD, it has lacked the ability to predict individual-level outcomes. PURPOSE: To address this problem, this paper has proposed an interpretable machine learning (ML) framework, including model-level assessment, feature-level assessment, and biology-level assessment to ensure a comprehensive analysis based on structural MRI of CD. METHODS: The ML framework has effectively identified the changes in brain regions in the stage of model-level assessment, verified the effectiveness of these altered brain regions to predict CD from normal controls in the stage of feature-level assessment, and carried out a correlation analysis between altered brain regions and clinical symptoms in the stage of biology-level assessment. RESULTS: The experimental results of this study have demonstrated that the Insula, Fusiform gyrus, Superior frontal gyrus, Precuneus, and the opercular portion of the Inferior frontal gyrus of CD showed significant alterations in brain regions. Furthermore, our study has revealed significant correlations between clinical symptoms and the frontotemporal lobes, insulin, and olfactory cortex, which also have been confirmed by previous studies. CONCLUSIONS: The ML framework proposed in this study exhibits exceptional potential in uncovering the intricate pathophysiological mechanisms underlying CD, with potential applicability in diagnosing other diseases.

In Situ Construction of a Hydrophobic Honeycomb-like Structured ZnMoO4 Coating Applied for Enhancing Zinc Anode Performance.

Aqueous zinc-ion batteries (AZIBs) suffer from sharp cycling deterioration due to serious interfacial side reactions and corrosion problems on the zinc anode. Herein, an efficacious approach to construct hydrophobic ZnMoO4 coatings on Zn (denoted as Zn@ZMO) is proposed to mitigate direct contact between the zinc anode and electrolyte and enhance its cycle life. The hydrophobic ZnMoO4 layer (contact angle = 128°) with a honeycomb-like structure is prepared by an in situ liquid phase deposition method. The as-prepared ZnMoO4 coating exhibits persistent corrosion protection for Zn through 30 days of immersion in a 2 M ZnSO4 electrolyte, indicating excellent stability of the ZnMoO4 layer and ensuring its available application in AZIBs. Unique microchannels in this kind of honeycomb-like structured coating favor Zn2+ ion diffusion and ease of ion transport, especially at high current cycling. Its robust surface exclusion can effectively counter other side reactions induced by water, simultaneously. As a result, the Zn@ZMO symmetrical cell shows a remarkable cycle lifespan exceeding 2700 h at 1 mA cm-2/1 mA h cm-2, surpassing that of the bare zinc cell by more than 100 folds. At a current density of 5 A g-1, the Zn@ZMO//V2O5 cell can still achieve a specific capacity of 167.0 mA h g-1 after 500 cycles with a capacity retention rate of 88%, which demonstrates its long-term cycling stability.

A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles.

N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.

Hypoxia-induced TREM1 promotes mesenchymal-like states of glioma stem cells via alternatively activating tumor-associated macrophages.

The mesenchymal subtype of glioblastoma (GBM) cells characterized by aggressive invasion and therapeutic resistance is thought to be dependent on cell-intrinsic alteration and extrinsic cellular crosstalk. Tumor-associated macrophages (TAMs) are pivotal in tumor progression, chemo-resistance, angiogenesis, and stemness maintenance. However, the impact of TAMs on the shifts in glioma stem cells (GSCs) states remains largely uncovered. Herein, we showed that the triggering receptor expressed on myeloid cells-1 (TREM1) preferentially expressed by M2-like TAMs and induced GSCs into mesenchymal-like states by modulating the secretion of TGFß2, which activated the TGFßR/SMAD2/3 signaling in GSCs. Furthermore, we demonstrated that TREM1 was transcriptionally regulated by HIF1a under the hypoxic environment and thus promoted an immunosuppressive type of TAMs via activating the TLR2/AKT/mTOR/c-MYC axis. Collectively, this study reveals that cellular communication between TAMs and GSCs through the TREM1-mediated TGFß2/TGFßR axis is involved in the mesenchymal-like transitions of GSCs. Our study provides valuable insights into the regulatory mechanisms between the tumor immune microenvironment and the malignant characteristics of GBM, which can lead to potential novel strategies targeting TAMs for tumor control.

Innovative Techniques in Video-Assisted Thoracoscopic Surgery: Lu's Approach.

Purpose: Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from Uniportal Video-Assisted Thoracoscopic Surgery(UVATS), is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach. Patients and Methods: The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected and analyzed. Patients were divided into the LVATS group and the UVATS group. Propensity score matching (PSM) was used to reduce selection bias and create two comparable groups. Perioperative variables were compared, and a p-value < 0.05 was deemed statistically significant. Results: A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144) min, P <0.001), less intraoperative blood loss (20 (20, 30) VS 25 (20, 50) mL, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50) cm, P <0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600) mL, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected (5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4) days, P =0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6) days, P = 0.608), VAS on the POD1 (4 (4, 4) VS 4 (4, 4), P=0.058) and POD3 (3 (3, 4) VS 4 (3, 4), P=0.219), and incidence of postoperative complications (P=0.521) between the two groups. Conclusion: Lu's approach for video-assisted thoracoscopic lobectomy is safe and feasible, potentially reducing surgery time, incision length, and intraoperative blood loss.

Hypoxia-inducible PRMT2 addiction in glioblastomas.

Hypoxia-inducible transcription factors (HIFs) are key transcription factors for cellular response to low oxygen levels. However, the specific mediators responsible for activating downstream transcription are not well characterized. We previously identified Protein Arginine methyltransferase 2 (PRMT2), a highly expressed methyltransferase in glioblastoma multiforme, as a transcription co-activator. And we established a connection between PRMT2-mediated histone H3R8 asymmetric methylation (H3R8me2a) and transcription activation. Here we find that PRMT2 is activated by HIF1α under hypoxic conditions. And we demonstrate that PRMT2 and its H3R8me2a activity are required for the transcription activation of a significant subset of hypoxia-induced genes. Consequently, the inactivation of PRMT2 suppresses hypoxia-induced glioblastoma cell migration, attenuates tumor progression, and enhances chemotherapeutic sensitivity in mouse xenograft models. In addition, our analysis of clinical glioma specimens reveals a correlation between PRMT2 protein levels, HIF1α abundance, and an unfavorable prognosis. Our study establishes HIF1α-induced PRMT2 as a critical modulator in the activation of hypoxia-related transcriptional programs, ultimately driving malignant progression.

O-arm guided minimally invasive resection of intrathoracic epidural schwannoma: how I do it.

BACKGROUND: Schwannomas are the most common intrathoracic neurogenic tumors. In the past, they were often treated by traditional open surgery. Video-assisted thoracic surgery (VATS) has also been used for some large tumors. Recently, minimally invasive posterior neurosurgical technique provides a new option for some of these tumors. METHOD: Here, we describe the specific steps involved in the O-arm guided minimally invasive removal of intrathoracic epidural schwannoma, as well as its advantages and limitations. CONCLUSION: O-arm guided minimally invasive resection of intrathoracic epidural schwannoma is safe and effective and causes little damage.

Solvation Structure Regulation for Highly Reversible Aqueous Al Metal Batteries.

Metallic Al has been deemed an ideal electrode material for aqueous batteries by virtue of its abundance and high theoretical capacity (8056 mAh cm-3). However, the development of aqueous Al metal batteries has been hindered by several side reactions, including water decomposition, Al corrosion, and passivation, which arise from the solvation reaction of Al and H2O in conventional aqueous electrolytes. In this work, we report that water activity in electrolyte can be suppressed by optimizing the Al3+ solvation structure through intercalation of polar pyridine-3-carboxylic acid in an aluminum trifluoromethanesulfonate aqueous environment. Furthermore, the pyridine-3-carboxylic acid molecules are inclined to alter the surface energy of Al, thus suppressing the random deposition of Al. As a result, the Al corrosion in the hybrid electrolyte is restrained, and the long-term electrochemical stability of the electrolyte is tremendously improved. These merits bring remarkable reversibility to aqueous Al batteries using Al-preintercalated MnO2 cathodes, delivering a retaining energy density of >250 Wh kg-1 at 0.2 A g-1 after 600 cycles.

Adsorption and reduction of Cr(VI) by N, S co-doped porous carbon from sewage sludge and low-rank coal: Combining experiments and theoretical calculations.

Herein, a novel N, S co-doped porous carbon (S5C5-AC) for Cr(VI) removal was prepared by co-hydrothermal carbonization (HTC) of sewage sludge (SS) and low-rank coal (LC) combining with KOH modification. The results showed that S5C5-AC had excellent adsorption performance on Cr(VI), and lower pH value, higher initial concentration and longer contact time were beneficial for Cr(VI) adsorption. The adsorption kinetics and isotherms revealed that Cr(VI) adsorption by S5C5-AC was homogeneous and dominated by chemisorption. The adsorption isotherm showed that the maximum equilibrium adsorption capacity of S5C5-AC for Cr(VI) was 382.04 mg/g at 25 °C. Furthermore, the results showed that the main mechanisms for Cr(VI) removal were the pore filling, electrostatic interaction and reduction. Moreover, the electron transfer mechanism during the adsorption and reduction process was further explored at the molecular and electronic levels by density functional theory (DFT) and front orbital theory (FOT) simulations. The analysis of DFT and FOT indicated that the synergistic effect between S and N functional groups was exhibited during the Cr(VI) removal process. Considering the existence of synergistic effects between N and S functional groups during adsorption, the S and N content and form were modified collaboratively. Increasing the relative content of pyrrolic N may be the most effective pathway for improving removal performance. Besides that, S5C5-AC exhibited excellent adsorption capacity over a high coexisting ion concentration range and various actual water bodies and regeneration performance, which indicated that S5C5-AC had promising potential for the remediation of wastewater in industrial applications.

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

A nomogram for predicting the risk of major postoperative complications for patients with meningioma.

PURPOSE: To identify risk factors for major postoperative complications in meningioma patients and to construct and validate a nomogram that identify patients at high risk of these complications. METHODS: The medical records of meningioma patients who underwent surgical resection in our hospital from January 2018 to December 2020 were collected. The patients were divided into a training set (815 cases from the main campus in 2018 and 2019) and a validation set (300 cases from two other campuses in 2020). Major postoperative complications were defined as any new neurological deficits and complications classified as Clavien-Dindo Grading (CDG) II or higher. Univariate and multivariate analyses were conducted using the training set to identify independent risk factors. A nomogram was constructed based on these results. And then validated the nomogram through bootstrap re-sampling in both the training and validation sets. The concordance index (C-index) and the area under the curve (AUC) were used to assess the discriminative ability of the nomogram. The Hosmer-Lemeshow test was performed to evaluate the goodness-of-fit. The optimal cutoff point for the nomogram was calculated using Youden's index. RESULTS: In the training set, 135 cases (16.56%) experienced major postoperative complications. The independent risk factors identified were male sex, recurrent tumors, American Society of Anesthesiologists (ASA) class III-IV, preoperative Karnofsky Performance Scale (KPS) score < 80, preoperative serum albumin < 35 g/L, tumor in the skull base or central sulcus area, subtotal tumor resection (STR), allogeneic blood transfusion, and larger tumor size. A nomogram was constructed based on these risk factors. It demonstrated good predictive performance, with a C-index of 0.919 for the training set and 0.872 for the validation set. The area under the curve (AUC) > 0.7 indicated satisfactory discriminative ability. The Hosmer-Lemeshow test showed no significant deviation from the predicted probabilities. And the cutoff for nomogram total points was about 200 (specificity 0.881 and sensitivity 0.834). CONCLUSIONS: The constructed nomogram demonstrated robust predictive performance for major postoperative complications in meningioma patients. This model can be used by surgeons as a reference in clinical decision-making.

Rare giant ovarian metastasis arising from a small primary lung adenocarcinoma: a case report.

This intricate case report details an exceptionally rare incidence of ovarian metastasis originating from a primary lung adenocarcinoma (LUAD). The relative rarity of this metastatic pathway in medical literature indicates significant diagnostic challenges. This patient was initially found to have both the ovarian tumor and lung nodule and they were originally considered independent primary tumors, derived from radiological interpretations and biomarker profiling. Nevertheless, subsequent postoperative histopathological and immunohistochemical staining evaluations identified ovarian tumors as invasive adenocarcinoma metastasized from lung. The lung and ovary tumor both showed marked anaplastic lymphoma kinase gene (ALK) protein expression by immunohistochemistry. The molecular pathologic genetic testing for lung tumor also revealed ALK rearrangement positive. The complexity of this case underscores the essentiality of maintaining a high degree of diagnostic vigilance, particularly when confronting synchronous tumors. In addition, immunohistochemical staining plays an important role in diagnosing the ovarian neoplasm's metastatic nature and determining the primary site of metastatic adenocarcinoma. For lung cancer with ovary metastasis patients, the adopting an adaptable treatment approach responsive to evolving diagnostic evidence can improve the accuracy of diagnosis and avoid excessive treatment of patients.

EGFR alterations in glioblastoma play a role in antitumor immunity regulation.

The epidermal growth factor receptor (EGFR) is the most frequently altered gene in glioblastoma (GBM), which plays an important role in tumor development and anti-tumor immune response. While current molecular targeted therapies against the EGFR signaling pathway and its downstream key molecules have not demonstrated favorable clinical outcomes in GBM. Whereas tumor immunotherapies, especially immune checkpoint inhibitors, have shown durable antitumor responses in many cancers. However, the clinical efficacy is limited in patients carrying EGFR alterations, indicating that EGFR signaling may involve tumor immune response. Recent studies reveal that EGFR alterations not only promote GBM cell proliferation but also influence immune components in the tumor microenvironment (TME), leading to the recruitment of immunosuppressive cells (e.g., M2-like TAMs, MDSCs, and Tregs), and inhibition of T and NK cell activation. Moreover, EGFR alterations upregulate the expression of immunosuppressive molecules or cytokines (such as PD-L1, CD73, TGF-ß). This review explores the role of EGFR alterations in establishing an immunosuppressive TME and hopes to provide a theoretical basis for combining targeted EGFR inhibitors with immunotherapy for GBM.

Evaluation of the Association Between Coronary Artery Aneurysms and Concomitant Infection in Patients With Kawasaki Disease.

We analyzed the relationship between recovery from coronary artery aneurysms (CAAs) and concurrent infections in patients with Kawasaki disease (KD). The estimated median time of aneurysm persistence between patients with and without infections was compared using Kaplan-Meier survival analyses. Risk factors associated with persistent CAAs at 2 years were identified using multivariable analyses. Co-infection was confirmed in 20.5% (106/518) of patients diagnosed with KD. No significant differences regarding treatment or coronary artery outcome were identified between patients with and without infections. The estimated median time of aneurysm persistence was higher in the co-infected group (9 vs. 6 months). A maximum Z-score ≥ 4.00 at 1 month had 78% sensitivity and 83% specificity in predicting CAAs without recovery within 1 year of onset, whereas the predictability was higher within 2 years of onset, with a Z-score ≥ 4.88 (sensitivity, 92%; specificity, 91%). Concomitant infections did not affect the response to treatment or coronary artery outcomes in patients with KD.

The non-invasive evaluation technique of patellofemoral joint stress: a systematic literature review.

Introduction: Patellofemoral joint stress (PFJS) is an important parameter for understanding the mechanism of patellofemoral joint pain, preventing patellofemoral joint injury, and evaluating the therapeutic efficacy of PFP rehabilitation programs. The purpose of this systematic review was to identify and categorize the non-invasive technique to evaluate the PFJS. Methods: Literature searches were conducted from January 2000 to October 2022 in electronic databases, namely, PubMed, Web of Science, and EBSCO (Medline, SPORTDiscus). This review includes studies that evaluated the patellofemoral joint reaction force (PJRF) or PFJS, with participants including both healthy individuals and those with patellofemoral joint pain, as well as cadavers with no organic changes. The study design includes cross-sectional studies, case-control studies, and randomized controlled trials. The JBI quality appraisal criteria tool was used to assess the risk of bias in the included studies. Results: In total, 5016 articles were identified in the database research and the citation network, and 69 studies were included in the review. Discussion: Researchers are still working to improve the accuracy of evaluation for PFJS by using a personalized model and optimizing quadriceps muscle strength calculations. In theory, the evaluation method of combining advanced computational and biplane fluoroscopy techniques has high accuracy in evaluating PFJS. The method should be further developed to establish the "gold standard" for PFJS evaluation. In practical applications, selecting appropriate methods and approaches based on theoretical considerations and ecological validity is essential.

Nasal and Sellar Anatomic Variations in Pituitary-Dependent Cushing Disease.

OBJECTIVE: Adrenocorticotrophic hormone excessive secretion in pituitary-dependent Cushing disease (CD) patients may lead to anatomic variations of the nasal-sphenoidal corridor as a result of hormone-induced abnormal soft tissue change. However, there is still a lack of data on anatomic dimensions in CD patients. In this study, magnetic resonance images were analyzed to determine the anatomic variations of the nasal cavity and sphenoid sinus in CD patients. METHODS: A retrospective radiographic analysis was conducted on CD patients undergoing endonasal transsphenoidal surgery as primary treatment between January 2013 and December 2017. A total of 97 CD patients and 100 controls were included. The nasal and sphenoidal anatomic dimensions of CD patients were compared with the control group. RESULTS: Both sides of nasal cavity height, middle nasal meatus width, and inferior nasal meatus width in CD patients were narrower than that of controls. When compared with controls, the ratio of the middle turbinate to middle nasal meatus and the ratio of inferior turbinate to inferior nasal meatus was found to increase on both sides in CD patients. Intercarotid distance of CD patients was shorter than that of controls. The most prevalent pneumatization pattern of CD patients was postsellar, followed by sellar, presellar, and conchal. CONCLUSIONS: Cushing disease patients have nasal and sphenoidal anatomic variations affecting the endonasal transsphenoidal surgical corridor, especially the shorter intercarotid distance. The neurosurgeon should be aware of these anatomic variations, and adapt surgical techniques and optimal approaches to reach the sella safely.

A Review of Artificial Intelligence in the Rupture Risk Assessment of Intracranial Aneurysms: Applications and Challenges.

Intracranial aneurysms (IAs) are highly prevalent in the population, and their rupture poses a significant risk of death or disability. However, the treatment of aneurysms, whether through interventional embolization or craniotomy clipping surgery, is not always safe and carries a certain proportion of morbidity and mortality. Therefore, early detection and prompt intervention of IAs with a high risk of rupture is of notable clinical significance. Moreover, accurately predicting aneurysms that are likely to remain stable can help avoid the risks and costs of over-intervention, which also has considerable social significance. Recent advances in artificial intelligence (AI) technology offer promising strategies to assist clinical trials. This review will discuss the state-of-the-art AI applications for assessing the rupture risk of IAs, with a focus on achievements, challenges, and potential opportunities.

Early Brain Injury and Neuroprotective Treatment after Aneurysmal Subarachnoid Hemorrhage: A Literature Review.

Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, such as microvascular alterations in brain tissue, ionic imbalances, blood-brain barrier disruption, immune-inflammatory responses, oxidative stress, and activation of cell death pathways. Research progress presents a variety of promising therapeutic approaches for the preservation of neurological function following SAH, including calcium channel antagonists, endothelin-1 receptor blockers, antiplatelet agents, anti-inflammatory agents, and anti-oxidative stress agents. EBI can be mitigated following SAH through neuroprotective measures. To enhance our comprehension of the relevant molecular pathways involved in brain injury, including brain ischemia-hypoxic injury, neuroimmune inflammation activation, and the activation of various cell-signaling pathways, following SAH, it is essential to investigate the evolution of these multifaceted pathophysiological processes. Facilitating neural repair following a brain injury is critical for improving patient survival rates and quality of life.

FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells.

BACKGROUND: Glioma stem cells (GSCs) are a subpopulation of tumor cells with self-renewal and tumorigenic capabilities in glioblastomas (GBMs). Diffuse infiltration of GSCs facilitates tumor progression and frustrates efforts at effective treatment. Further compounding this situation is the currently limited understanding of what drives GSC invasion. Here we comprehensively evaluated the significance of a novel invasion-related protein, Family with Sequence Similarity 129 Member A (FAM129A), in infiltrative GSCs. METHODS: Western blotting, immunohistochemistry, and gene expression analysis were used to quantify FAM129A in glioma specimens and cancer datasets. Overexpression and knockdown of FAM129A in GSCs were used to investigate its effects on tumor growth and invasion. RNA-seq, qRT-PCR, western blotting, and co-precipitation assays were used to investigate FAM129A signaling mechanisms. RESULTS: FAM129A is preferentially expressed in invasive frontiers. Targeting FAM129A impairs GSC invasion and self-renewal. Mechanistically, FAM129A acted as a positive regulator of Notch signaling by binding with the Notch1 intracellular domain (NICD1) and preventing its degradation. CONCLUSIONS: FAM129A and NICD1 provide a precise indicator for identifying tumor margins and aiding prognosis. Targeting them may provide a significantly therapeutic strategy for GSCs.