Multi-instance learning for identifying high-risk subregions associated with synchronous distant metastasis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common histological subtypes of renal tumors. PURPOSE: To identify high-risk subregions associated with synchronous distant metastasis. METHODS: This study enrolled a total of 277 patients with ccRCC. Voxel intensity and local entropy values were compiled within the region of interest for all patients. Unsupervised k-means clustering yielded three subregions per tumor. Radiomic features were extracted, and random forest-based feature selection was conducted. The selected features were used in a multi-instance support vector machine (mi-SVM) model for training, and predictions were made on the validation cohort. Model performance was evaluated using five-fold cross-validation. The subregion with the highest score for patients with synchronous distant metastasis was identified across all cohorts. RESULTS: The mi-SVM model yielded an average area under the curve (AUC) of 0.812 in the training cohort and 0.805 in the validation cohort. In the entire cohort of patients with synchronous distant metastasis, subregion 2, characterized by tumor periphery and intratumoral transitional components, accounted for the highest proportion (48.57%, 30.6/63) among all subregions. It represents a high-risk subregion for synchronous distant metastasis of clear cell renal cell carcinoma. CONCLUSION: The peripheral and intratumoral transition zones of clear cell renal cell carcinoma are high-risk subregions associated with synchronous distant metastasis.

The use of organoids in creating immune microenvironments and treating gynecological tumors.

Owing to patient-derived tumor tissues and cells, significant advances have been made in personalized cancer treatment and precision medicine, with cancer stem cell-derived three-dimensional tumor organoids serving as crucial in vitro models that accurately replicate the structural, phenotypic, and genetic characteristics of tumors. However, despite their extensive use in drug testing, genome editing, and transplantation for facilitating personalized treatment approaches in clinical practice, the inadequate capacity of these organoids to effectively model immune cells and stromal components within the tumor microenvironment limits their potential. Additionally, effective clinical immunotherapy has led the tumor immune microenvironment to garner considerable attention, increasing the demand for simulating patient-specific tumor-immune interactions. Consequently, co-culture techniques integrating tumor organoids with immune cells and tumor microenvironment constituents have been developed to expand the possibilities for personalized drug response investigations, with recent advancements enhancing the understanding of the strengths, limitations, and applicability of the co-culture approach. Herein, the recent advancements in the field of tumor organoids have been comprehensively reviewed, specifically highlighting the tumor organoid co-culture-related developments with various immune cell models and their implications for clinical research. Furthermore, this review delineates the current state of research and application of organoid models regarding the therapeutic approaches and related challenges for gynecological tumors. This study may provide a theoretical basis for further research on the use of patient-derived organoids in tumor immunity, drug development, and precision medicine.

Factors Associated With the Spatial Distribution of Severe Fever With Thrombocytopenia Syndrome in Zhejiang Province, China: Risk Analysis Based on Maximum Entropy.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was first identified in mainland China in 2009 and has been reported in Zhejiang Province, China, since 2011. However, few studies have focused on the association between ticks, host animals, and SFTS. Objective: In this study, we analyzed the influence of meteorological and environmental factors as well as the influence of ticks and host animals on SFTS. This can serve as a foundational basis for the development of strategic policies aimed at the prevention and control of SFTS. Methods: Data on SFTS incidence, tick density, cattle density, and meteorological and environmental factors were collected and analyzed using a maximum entropy-based model. Results: As of December 2019, 463 laboratory-confirmed SFTS cases were reported in Zhejiang Province. We found that the density of ticks, precipitation in the wettest month, average temperature, elevation, and the normalized difference vegetation index were significantly associated with SFTS spatial distribution. The niche model fitted accurately with good performance in predicting the potential risk areas of SFTS (the average test area under the receiver operating characteristic curve for the replicate runs was 0.803 and the SD was 0.013). The risk of SFTS occurrence increased with an increase in tick density, and the response curve indicated that the risk was greater than 0.5 when tick density exceeded 1.4. The risk of SFTS occurrence decreased with increased precipitation in the wettest month, and the risk was less than 0.5 when precipitation exceeded 224.4 mm. The relationship between elevation and SFTS occurrence showed a reverse V shape, and the risk peaked at approximately 400 m. Conclusions: Tick density, precipitation, and elevation were dominant influencing factors for SFTS, and comprehensive intervention measures should be adjusted according to these factors to reduce SFTS incidence in Zhejiang Province.

Identification of human papillomavirus and Rb/E2F pathway genomic alterations in mixed adeno-neuroendocrine carcinoma.

OBJECTIVE: To investigate the molecular characteristics of Rb/E2F in mixed adeno-neuroendocrine carcinoma (MANEC). MATERIALS AND METHODS: The clinicopathological features of MANEC were analyzed. The protein expressions of Rb, p16, and p53 were detected by the immunohistochemical method. The infection status of high-risk human papillomavirus (HR-HPV) was evaluated by in situ hybridization (ISH) and the gene chip method. RESULTS: Thirteen cases of MANEC were divided into four molecular patterns according to Rb protein expression and HPV status. Group 1: A total of eight of the 13 cases showed positive Rb protein expression and lack of HR-HPV expression (8/13, 62%). Rb protein expression with p16 protein deletion and p53 protein abnormal expression was unique to NEC. Group 2: three cases (3/13, 23%) with negative Rb protein expression and lack of HR-HPV expression. Group 3: There was one case (1/13, 8%) with positive expression of Rb protein accompanied by HR-HPV. Group 4: There was one case of Rb protein loss with an HR-HPV-positive status. CONCLUSIONS: HR-HPV and Rb/p16/p53 pathway can be associated in MANEC pathogenesis, which provides the research basis for personalized treatment of MANEC.

Delay the progression of glucocorticoid-induced osteoporosis: Fraxin targets ferroptosis via the Nrf2/GPX4 pathway.

Glucocorticoid-induced osteoporosis (GIOP) commonly accelerates bone loss, increasing the risk of fractures and osteonecrosis more significantly than traditional menopausal osteoporosis. The extracellular environment influenced by glucocorticoids heightens fracture and osteonecrosis risks. Fraxin (Fra), a key component of the traditional Chinese herbal remedy Cortex Fraxini, is known for its wide-ranging pharmacological effects, but its impact on GIOP remains unexplored. This investigation aims to delineate the effects and underlying mechanisms of Fra in combating dexamethasone (Dex)-induced ferroptosis and GIOP. We established a mouse model of GIOP via intraperitoneal injections of Dex and cultured osteoblasts with Dex treatment for in vitro analysis. We evaluated the impact of Fra on Dex-treated osteoblasts through assays such as C11-BODIPY and FerroOrange staining, mitochondrial functionality tests, and protein expression analyses via Western blot and immunofluorescence. The influence of Fra on bone microarchitecture of GIOP in mice was assessed using microcomputerized tomography, hematoxylin and eosin staining, double-labeling with Calcein-Alizarin Red S, and immunohistochemistry at imaging and histological levels. Based on our data, Fra prevented Dex-induced ferroptosis and bone loss. In vitro, glutathione levels increased and malondialdehyde, lipid peroxidation, and mitochondrial reactive oxygen species decreased. Fra treatment also increases nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and COL1A1 expression and promotes bone formation. To delve deeper into the mechanism, the findings revealed that Fra triggered the activation of Nrf2/GPX4 signaling. Moreover, the use of siRNA-Nrf2 blocked the beneficial effect of Fra in osteoblasts cultivated with Dex. Fra effectively combats GIOP by activating the Nrf2/GPX4 signaling pathway to inhibit ferroptosis.

Circular RNA IGF1R Promotes Cardiac Repair via Activating ß-Catenin Signaling by Interacting with DDX5 in Mice after Ischemic Insults.

The potential of circular RNAs (circRNAs) as biomarkers and therapeutic targets is becoming increasingly evident, yet their roles in cardiac regeneration and myocardial renewal remain largely unexplored. Here, we investigated the function of circIGF1R and related mechanisms in cardiac regeneration. Through analysis of circRNA sequencing data from neonatal and adult cardiomyocytes, circRNAs associated with regeneration were identified. Our data showed that circIGF1R expression was high in neonatal hearts, decreased with postnatal maturation, and up-regulated after cardiac injury. The elevation was validated in patients diagnosed with acute myocardial infarction (MI) within 1 week. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and myocardial tissue from mice after apical resection and MI, we observed that circIGF1R overexpression enhanced cardiomyocyte proliferation, reduced apoptosis, and mitigated cardiac dysfunction and fibrosis, while circIGF1R knockdown impeded endogenous cardiac renewal. Mechanistically, we identified circIGF1R binding proteins through circRNA precipitation followed by mass spectrometry. RNA pull-down Western blot and RNA immunoprecipitation demonstrated that circIGF1R directly interacted with DDX5 and augmented its protein level by suppressing ubiquitin-dependent degradation. This subsequently triggered the ß-catenin signaling pathway, leading to the transcriptional activation of cyclin D1 and c-Myc. The roles of circIGF1R and DDX5 in cardiac regeneration were further substantiated through site-directed mutagenesis and rescue experiments. In conclusion, our study highlights the pivotal role of circIGF1R in facilitating heart regeneration and repair after ischemic insults. The circIGF1R/DDX5/ß-catenin axis emerges as a novel therapeutic target for enhancing myocardial repair after MI, offering promising avenues for the development of regenerative therapies.

Rapid nanomolar detection of cocaine in biofluids by electrochemical aptamer-based sensor with low-temperature effect for drugged driving screening.

Cocaine is one of the most abused illicit drugs, and its abuse damages the central nervous system and can even lead directly to death. Therefore, the development of simple, rapid and highly sensitive detection methods is crucial for the prevention and control of drug abuse, traffic accidents and crime. In this work, an electrochemical aptamer-based (EAB) sensor based on the low-temperature enhancement effect was developed for the direct determination of cocaine in bio-samples. The signal gain of the sensor at 10 °C was greatly improved compared to room temperature, owing to the improved affinity between the aptamer and the target. Additionally, the electroactive area of the gold electrode used to fabricate the EAB sensor was increased 20 times by a simple electrochemical roughening method. The porous electrode possesses more efficient electron transfer and better antifouling properties after roughening. These improvements enabled the sensor to achieve rapid detection of cocaine in complex bio-samples. The low detection limits (LOD) of cocaine in undiluted urine, 50% serum and 50% saliva were 70 nM, 30 nM and 10 nM, respectively, which are below the concentration threshold in drugged driving screening. The aptasensor was simple to construct and reusable, which offers potential for drugged driving screening in the real world.

Socioeconomic Status Plays a Moderating Role in the Association Between Multimorbidity and Health-Related Quality of Life Among Cancer Patients.

This study aimed to explore the moderating role of socioeconomic status (SES) in the association between multimorbidity and health-related quality of life (HRQOL) among cancer patients in Anhui China. A total of 560 cancer patients were recruited for the cross-section study. Socio-demographic and clinical characteristics were analyzed using descriptive statistics. Tobit regression analysis was employed to investigate the relationship between multimorbidity and HRQOL as well as to assess the moderating effect of SES. The research findings indicated that 76.61% of cancer patients experienced multimorbidity, with psychological multimorbidity being the most prevalent (45.54%), followed by physical-psychological multimorbidity (20.89%). Moreover, physical-psychological multimorbidity had the most substantial adverse effect on HRQOL (P < .001). The presence of multimorbidity was correlated with a significant decline in HRQOL, with a 17.5% (P < .001) decrease in HRQOL for each additional multimorbidity. Additionally, SES played a significant role in moderating the impact of multimorbidity on HRQOL in cancer patients. (Marginal effect = -0.022, P < .01). The high SES group exhibited a higher overall HRQOL than the low SES group (Marginal effect = 0.068, P < .001). And with the increase of multimorbidity, HRQOL in the higher SES showed a more pronounced downward trend, compared with the lower SES (ß = -.270 vs ß = -.201, P < .001). Our findings underscore the importance of preventing and managing multimorbidity in cancer patients, particularly those with low SES. Furthermore, it is essential to consider the impact of the rapid decline in HRQOL as the number of multimorbidity increases in individuals with higher SES. It is imperative to explore interdisciplinary and continuous collaborative management models.

Plant responses to abiotic stress regulated by histone acetylation.

In eukaryotes, histone acetylation and deacetylation play an important role in the regulation of gene expression. Histone acetylation levels are reversibly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Increasing evidence highlights histone acetylation plays essential roles in the regulation of gene expression in plant response to environmental stress. In this review, we discussed the recent advance of histone acetylation in the regulation of abiotic stress responses including temperature, light, salt and drought stress. This information will contribute to our understanding of how plants adapt to environmental changes. As the mechanisms of epigenetic regulation are conserved in many plants, research in this field has potential applications in improvement of agricultural productivity.

PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Drug-coated balloon angioplasty for the treatment of intracranial arterial stenosis in a young stroke patient: A case report.

BACKGROUND: Intracranial arterial narrowing is a significant factor leading to brief episodes of reduced blood flow to the brain, known as transient ischemic attacks, or full-blown strokes. While atherosclerosis is commonly associated with intracranial arterial narrowing, it is frequently of a non-atherosclerotic nature in younger patients. CASE SUMMARY: Here, we present the case of a young stroke patient with narrowing of the middle cerebral artery (MCA), characterized as non-atherosclerotic lesions, who experienced an ischemic stroke despite receiving standard drug therapy. The patient underwent digital subtraction angiography (DSA) to assess the entire network of blood vessels in the brain, revealing significant narrowing (approximately 80%) in the M1 segment of the right MCA. Subsequently, the patient underwent Drug-Coated Balloon Angioplasty to treat the stenosis in the right MCA's M1 segment. Follow-up DSA confirmed the resolution of stenosis in this segment. Although the remaining branches showed satisfactory blood flow, the vessel wall exhibited irregularities. A review of DSA conducted six months later showed no evident stenosis in the right MCA, with a smooth vessel wall. CONCLUSION: The use of drug-coated balloon angioplasty demonstrated favorable outcomes in repairing and reshaping the blood vessel wall in young patients. Therefore, it may be considered a promising treatment option for similar cases.

The natural course, treatment outcomes, and long-term prognosis of cervical spinal cord arteriovenous shunts.

OBJECTIVE: The highly intricate nature of the cervical spinal cord can cause arteriovenous shunts in these segments that may be associated with heightened clinical risks and treatment complexities. In this article, the authors aimed to provide a comprehensive analysis of the detailed natural course, treatment, and clinical outcomes of cervical spinal cord arteriovenous shunts (SCAVSs) based on the largest cohort to date. METHODS: Two hundred forty consecutive patients were included. Data on clinical presentation, angioarchitecture, treatment, and follow-up were retrospectively reviewed. RESULTS: The cohort demonstrated a greater prevalence of acute onset (63.3% vs 36.7%). Spontaneous recovery was observed in 63.7% of patients after onset, with a significantly elevated recovery rate observed among patients experiencing acute onset (72.4% vs 48.9%, p < 0.001). The risks of acute and gradual clinical deterioration after onset was 11.9%/year and 13.4%/year, respectively. Microsurgery was performed in 39.6% of patients, while the remaining 60.4% exclusively underwent embolization. The complete obliteration rate was 65.3% after microsurgery and 21.4% after embolization. The rate of treatment-related deterioration was 14.7% after microsurgery and 6.2% after embolization. After partial treatment, the acute and gradual deterioration rates were 4.1%/year and 6.6%/year, respectively. Lack of spontaneous recovery after onset was an independent predictor of embolization-related deterioration (OR 17.905, p = 0.007) and long-term gradual deterioration after partial treatment (HR 2.325, p = 0.021). After a median follow-up period of 32.55 months, prognosis was unfavorable in 16.7% of patients, with the sole independent risk factor being the absence of spontaneous recovery after onset (OR 2.476, p = 0.018). CONCLUSIONS: The outcomes of patients with cervical SCAVS were generally favorable, even in patients with only partial obliteration of the lesions. However, patients who did not show a trend toward spontaneous recovery after onset had a significantly elevated risk of unfavorable prognosis, highlighting the need for prompt clinical intervention.

Recent Advances in Self-Powered Tactile Sensing for Wearable Electronics.

With the arrival of the Internet of Things era, the demand for tactile sensors continues to grow. However, traditional sensors mostly require an external power supply to meet real-time monitoring, which brings many drawbacks such as short service life, environmental pollution, and difficulty in replacement, which greatly limits their practical applications. Therefore, the development of a passive self-power supply of tactile sensors has become a research hotspot in academia and the industry. In this review, the development of self-powered tactile sensors in the past several years is introduced and discussed. First, the sensing principle of self-powered tactile sensors is introduced. After that, the main performance parameters of the tactile sensors are briefly discussed. Finally, the potential application prospects of the tactile sensors are discussed in detail.

Augmented microglial endoplasmic reticulum-mitochondria contacts mediate depression-like behavior in mice induced by chronic social defeat stress.

Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs' modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1CreER/+Hspa9f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice.

Mediating roles of activities of daily living and depression on the relationship between sleep quality and health-related quality of life.

This study aimed to explore the mediating effects of ADL and depression on the relationship between sleep quality and HRQOL among older people in rural China, while also exploring the moderating impact of loneliness. The study gathered data from a household survey conducted among 1587 Chinese rural older adults (mean age = 73.63 years). The collected data was analyzed using SPSS version 23.0 software (IBM, New York, USA) and the PROCESS macro version 4.0 program. The findings indicated a significant correlation between sleep quality, ADL, depression, loneliness and HRQOL. ADL and depression exhibited a chain mediation effect on the relationship between sleep quality and HRQOL. Notably, the association between sleep quality and HRQOL was entirely mediated by ADL and depression. Additionally, loneliness acted as a moderator in the relationship between ADL and HRQOL. The findings of this study suggest that interventions focusing on sleep quality should prioritize strategies for enhancing older adults' ADL and depression as integral components of promoting older adults' HRQOL.

Enantioselective copper-catalyzed azidation/click cascade reaction for access to chiral 1,2,3-triazoles.

Chiral 1,2,3-triazoles are highly attractive motifs in various fields. However, achieving catalytic asymmetric click reactions of azides and alkynes for chiral triazole synthesis remains a significant challenge, mainly due to the limited catalytic systems and substrate scope. Herein, we report an enantioselective azidation/click cascade reaction of N-propargyl-ß-ketoamides with a readily available and potent azido transfer reagent via copper catalysis, which affords a variety of chiral 1,2,3-triazoles with up to 99% yield and 95% ee under mild conditions. Notably, chiral 1,5-disubstituted triazoles that have not been accessed by previous asymmetric click reactions are also prepared with good functional group tolerance.

Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C-Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury.

BACKGROUND: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. METHODS AND RESULTS: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming. CONCLUSIONS: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Role of mitochondria-associated membranes in the hippocampus in the pathogenesis of depression.

BACKGROUND: Pathological changes, such as microglia activation in the hippocampus frequently occur in individuals with animal models of depression; however, they may share a common cellular mechanism, such as endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Mitochondria associated membranes (MAMs) are communication platforms between ER and mitochondria. This study aimed to investigate the role of intracellular stress responses, especially structural and functional changes of MAMs in depression. METHODS: We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS. RESULTS: CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice. LIMITATION: The cellular specificity of MAMs related protein changes in CSDS mice was not explored. CONCLUSIONS: In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression's pathophysiology. EA may improve depression by regulating intracellular stress responses.

Prognosis Prediction of Sudden Sensorineural Hearing Loss Using Ensemble Artificial Intelligence Learning Models.

OBJECTIVE: We used simple variables to construct prognostic prediction ensemble learning models for patients with sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Retrospectively study. SETTING: Tertiary medical center. PATIENTS: 1,572 patients with SSNHL. INTERVENTION: Prognostic. MAIN OUTCOME MEASURES: We selected four variables, namely, age, days after onset of hearing loss, vertigo, and type of hearing loss. We also compared the accuracy between different ensemble learning models based on the boosting, bagging, AdaBoost, and stacking algorithms. RESULTS: We enrolled 1,572 patients with SSNHL; 73.5% of them showed improving and 26.5% did not. Significant between-group differences were noted in terms of age ( p = 0.011), days after onset of hearing loss ( p < 0.001), and concurrent vertigo ( p < 0.001), indicating that the patients who showed improving to treatment were younger and had fewer days after onset and fewer vertigo symptoms. Among ensemble learning models, the AdaBoost algorithm, compared with the other algorithms, achieved higher accuracy (82.89%), higher precision (86.66%), a higher F1 score (89.20), and a larger area under the receiver operating characteristics curve (0.79), as indicated by test results of a dataset with 10 independent runs. Furthermore, Gini scores indicated that age and days after onset are two key parameters of the predictive model. CONCLUSIONS: The AdaBoost model is an effective model for predicting SSNHL. The use of simple parameters can increase its practicality and applicability in remote medical care. Moreover, age may be a key factor influencing prognosis.