Brains in sync, friends in empathy: interbrain neural mechanisms underlying the impact of interpersonal closeness on mutual empathy.

Many everyday empathetic experiences arise within our social interactions and depend significantly on interpersonal closeness. However, the interbrain processes underlying social-oriented empathy by interpersonal closeness remain unclear. To address this gap, we conducted a dyadic social judgement task with dyads of friends and strangers, where targets received social evaluative feedback and empathizers observed the scenario in different experimental trials. Results showed that dyads of friends exhibited greater affect sharing than strangers when witnessing their partners being accepted or rejected. This was supported by the more pronounced event-related potential similarity in friends during the 340-840 ms post-feedback window, mediating the link between interpersonal closeness and affect sharing. Furthermore, witnessing emotional feedback elicited greater interbrain neural synchronization of brain α-oscillation between the empathizer's left prefrontal cortex and the target's left temporoparietal junction in dyads of friends compared with those of strangers. This empathy-related synchronization was associated with mutual affect sharing within dyads of friends but not within dyads of strangers. Our findings highlight the sensitivity of empathy to interpersonal closeness, which links to sustained attention and detailed evaluation in social scenarios, along with functional communication between brain regions for mentalizing and emotional regulation. These insights have therapeutic potential for improving social functioning and relationship satisfaction.

Targeting auditory verbal hallucinations in schizophrenia: effective connectivity changes induced by low-frequency rTMS.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

Ultrasomics differentiation of malignant and benign focal liver lesions based on contrast-enhanced ultrasound.

OBJECTIVES: To establish a nomogram for differentiating malignant and benign focal liver lesions (FLLs) using ultrasomics features derived from contrast-enhanced ultrasound (CEUS). METHODS: 527 patients were retrospectively enrolled. On the training cohort, ultrasomics features were extracted from CEUS and b-mode ultrasound (BUS). Automatic feature selection and model development were performed using the Ultrasomics-Platform software, outputting the corresponding ultrasomics scores. A nomogram based on the ultrasomics scores from artery phase (AP), portal venous phase (PVP) and delayed phase (DP) of CEUS, and clinical factors were established. On the validation cohort, the diagnostic performance of the nomogram was assessed and compared with seniorexpert and resident radiologists. RESULTS: In the training cohort, the AP, PVP and DP scores exhibited better differential performance than BUS score, with area under the curve (AUC) of 84.1-85.1% compared with the BUS (74.6%, P < 0.05). In the validation cohort, the AUC of combined nomogram and expert was significantly higher than that of the resident (91.4% vs. 89.5% vs. 79.3%, P < 0.05). The combined nomogram had a comparable sensitivity with the expert and resident (95.2% vs. 98.4% vs. 97.6%), while the expert had a higher specificity than the nomogram and the resident (80.6% vs. 72.2% vs. 61.1%, P = 0.205). CONCLUSIONS: A CEUS ultrasomics based nomogram had an expert level performance in FLL characterization.

Association between serum magnesium concentrations and the risk of developing acute kidney injury in patients with cirrhosis: a retrospective cohort study based on the MIMIC-IV database.

BACKGROUND: In various disease contexts, magnesium abnormalities are associated with acute kidney injury (AKI) incidence. However, this association remains unclear and has not been systematically investigated in patients with cirrhosis. Hence, we aimed to elucidate the association between admission serum magnesium levels and AKI incidence in intensive care unit (ICU)-admitted cirrhotic patients. METHODS: A retrospective cohort study was conducted using MIMIC-IV2.2 data, focusing on critically ill patients with cirrhosis. We employed univariable and multivariable logistic regression and restricted cubic spline analyses to robustly address our research objectives. To further substantiate the findings, subgroup and sensitivity analyses were also conducted. RESULTS: Among the 3,228 enrolled ICU-admitted cirrhotic patients, 34.4% were female, and the overall AKI incidence was 68.6% (2,213/3,228). Multivariable logistic regression analysis revealed an independent relationship between elevated serum magnesium levels and increased AKI risk (OR = 1.55 [95% CI = 1.15-2.09], p = 0.004). Compared with individuals with serum magnesium levels < 1.6 mg/dL, individuals with serum magnesium levels in Q2 (1.6-2.6 mg/dL) and Q3 (≥2.6 mg/dL) had adjusted ORs for AKI of 1.89 (95% CI = 1.34-2.65, p < 0.001) and 2.19 (95% CI = 1.27-3.75, p = 0.005), respectively. The restricted cubic spline analysis revealed that AKI risk increased linearly with increasing serum magnesium levels. Subgroup analysis revealed that the association between serum magnesium levels and AKI incidence was remarkably stable in subgroup analysis (all Pinteraction >0.05). CONCLUSIONS: High serum magnesium concentrations were significantly associated with an increased AKI risk in ICU-admitted patients with cirrhosis. Further randomized trials are needed to confirm this association.

LncRNA MFRL regulates the phenotypic switch of vascular smooth muscle cells to attenuate arterial remodeling by encoding a novel micropeptide MFRLP.

BACKGROUND: Arterial remodeling is a common pathophysiological change in the pathogenesis of cardiovascular diseases in which the phenotypic switch of vascular smooth muscle cells (VSMC) plays an important role. Recently, an increasing number of long non-coding RNAs(lncRNAs) have been shown to encode micropeptides that play biological roles and have great clinical transformation potential. However, the role of micropeptides encoded by lncRNAs in arterial remodeling has not been well studied and requires further exploration. METHODS AND RESULTS: Through bioinformatic analysis and experimental verification, we found that a new lncRNA, the mitochondrial function-related lncRNA (MFRL), encodes a 64-amino acid micropeptide, MFRLP. MFRL and MFRLP play important roles in the phenotypic switch of VSMC. Further experiments showed that MFRLP interacts with mitochondrial cytochrome b to reduce accumulation of reactive oxygen species, suppress mitophagy and inhibit the VSMC switch from contractile to synthetic phenotype. CONCLUSIONS: LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling.

MicroRNA-30a inhibits cell proliferation in a sepsis-induced acute kidney injury model by targeting the YAP-TEAD complex.

Background: Acute kidney injury (AKI) is a primary feature of renal complications in patients with sepsis. MicroRNA (miRNA/miR)-30a is an essential regulator of cardiovascular diseases, tumors, phagocytosis, and other physical processes, but whether it participates in sepsis-induced AKI (sepsis-AKI) is unknown. We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI. Methods: The classical cecal ligation and puncture (CLP) method and lipopolysaccharide (LPS)-induced Human Kidney 2 (HK-2) cells were used to establish in vivo and in vitro sepsis-AKI models. Specific pathogen-free and mature male Sprague-Dawley (SD) rats, aged 6-8 weeks (weight 200-250 g), were randomly divided into five-time phase subgroups. Fluid resuscitation with 30 mL/kg 37 °C saline was administered after the operation, without antibiotics. Formalin-fixed, paraffin-embedded kidney sections were stained with hematoxylin and eosin. SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors, and compared with untreated normal controls. RNA, protein, and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and cell counting kit-8 methods. A Dual-Luciferase Assay Kit (Promega) was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics. Results: Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h (P <0.05). Tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were significantly increased in renal tissue 3 h after the operation in rats (P <0.05), and gradually decreased 6 h, 12 h, and 24 h after CLP. Levels of miR-30a-5p and miR-30a-3p were significantly down-regulated at 3 h after LPS treatment (P <0.05), and gradually decreased in HK-2 cells. One hour after LPS (10 µg/mL) treatment, TNF-α and IL-1ß levels in HK-2 cells were significantly up-regulated (P < 0.05), and they were markedly down-regulated after 3 h (P <0.05). IL-6 expression levels began to rise after LPS treatment of cells, peaked at 6 h (P <0.05), and then decreased to the initial level within a few hours. Stimulation with 10 µg/mL LPS promoted HK-2 cells proliferation, which was inhibited after miR-30a-3p-mimic transfection. Bioinformatics prediction identified 37 potential miR-30a-3p target genes, including transcriptional enhanced associate domain 1 (TEAD1). After transfection of HK-2 cells with miR-30a-3p mimics and miR-30a-3p inhibitor, TEAD1 transcript was significantly up- and down-regulated, respectively (both P <0.05). After LPS treatment (24 h), expression of TEAD1 in the inhibitors group was significantly increased (P <0.01), while that in the mimics group was significantly suppressed (P <0.01). In the dual luciferase reporter experiment, miR-30a-3p overexpression decreased fluorescence intensity (P <0.01) from TEAD1-wt-containing plasmids, but did not influence fluorescence intensity from TEAD1-muta-containing plasmids. LPS may promote HK-2 cells proliferation through the miR-30a-3p/TEAD1 pathway. Conclusion: In a background of expression of inflammatory factors, including TNF-α, IL-1ß, and IL-6, which were transiently increased in the sepsis-AKI model, miR-30a was down-regulated. Down-regulated miR-30a-3p may promote cell proliferation by targeting TEAD1 in LPS-induced HK-2 cells, demonstrating its potential as a biomarker for early sepsis-AKI diagnosis.

Development of a nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis.

In this study, we aimed to investigate the risk factors associated with in-hospital mortality in patients with cirrhosis and sepsis, establish and validate the nomogram. This retrospective study included patients diagnosed with liver cirrhosis and sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV). Models were compared by the area under the curve (AUC), integrated discriminant improvement (IDI), net reclassification index (NRI) and decision curve analysis (DCA). A total of 1,696 patients with cirrhosis and sepsis were included in the final cohort. Our final model included the following 9 variables: age, heartrate, total bilirubin (TBIL), glucose, sodium, anion gap (AG), fungal infections, mechanical ventilation, and vasopressin. The nomogram were constructed based on these variables. The AUC values of the nomograms were 0.805 (95% CI 0.776-0.833), which provided significantly higher discrimination compared to that of SOFA score [0.684 (95% CI 0.647-0.720)], MELD-Na [0.672 (95% CI 0.636-0.709)] and ABIC [0.674(95% CI 0.638-0.710)]. We established the first nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis based on these factors. This nomogram can performs well and facilitates clinicians to identify people at high risk of in-hospital mortality.

Japanese encephalitis virus NS1 and NS1' proteins induce vimentin rearrangement via the CDK1-PLK1 axis to promote viral replication.

The host cytoskeleton plays crucial roles in various stages of virus infection, including viral entry, transport, replication, and release. However, the specific mechanisms by which intermediate filaments are involved in orthoflavivirus infection have not been well understood. In this study, we demonstrate that the Japanese encephalitis virus (JEV) remodels the vimentin network, resulting in the formation of cage-like structures that support viral replication. Mechanistically, JEV NS1 and NS1' proteins induce the translocation of CDK1 from the nucleus to the cytoplasm and interact with it, leading to the phosphorylation of vimentin at Ser56. This phosphorylation event recruits PLK1, which further phosphorylates vimentin at Ser83. Consequently, these phosphorylation modifications convert the typically filamentous vimentin into non-filamentous "particles" or "squiggles." These vimentin "particles" or "squiggles" are then transported retrogradely along microtubules to the endoplasmic reticulum, where they form cage-like structures. Notably, NS1' is more effective than NS1 in triggering the CDK1-PLK1 cascade response. Overall, our study provides new insights into how JEV NS1 and NS1' proteins manipulate the vimentin network to facilitate efficient viral replication. IMPORTANCE: Japanese encephalitis virus (JEV) is a mosquito-borne orthoflavivirus that causes severe encephalitis in humans, particularly in Asia. Despite the availability of a safe and effective vaccine, JEV infection remains a significant public health threat due to limited vaccination coverage. Understanding the interactions between JEV and host proteins is essential for developing more effective antiviral strategies. In this study, we investigated the role of vimentin, an intermediate filament protein, in JEV replication. Our findings reveal that JEV NS1 and NS1' proteins induce vimentin rearrangement, resulting in the formation of cage-like structures that envelop the viral replication factories (RFs), thus facilitating efficient viral replication. Our research highlights the importance of the interplay between the cytoskeleton and orthoflavivirus, suggesting that targeting vimentin could be a promising approach for the development of antiviral strategies to inhibit JEV propagation.

Collaborative Enhancement of Consistency and Accuracy in US Diagnosis of Thyroid Nodules Using Large Language Models.

Background Large language models (LLMs) hold substantial promise for medical imaging interpretation. However, there is a lack of studies on their feasibility in handling reasoning questions associated with medical diagnosis. Purpose To investigate the viability of leveraging three publicly available LLMs to enhance consistency and diagnostic accuracy in medical imaging based on standardized reporting, with pathology as the reference standard. Materials and Methods US images of thyroid nodules with pathologic results were retrospectively collected from a tertiary referral hospital between July 2022 and December 2022 and used to evaluate malignancy diagnoses generated by three LLMs-OpenAI's ChatGPT 3.5, ChatGPT 4.0, and Google's Bard. Inter- and intra-LLM agreement of diagnosis were evaluated. Then, diagnostic performance, including accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), was evaluated and compared for the LLMs and three interactive approaches: human reader combined with LLMs, image-to-text model combined with LLMs, and an end-to-end convolutional neural network model. Results A total of 1161 US images of thyroid nodules (498 benign, 663 malignant) from 725 patients (mean age, 42.2 years ± 14.1 [SD]; 516 women) were evaluated. ChatGPT 4.0 and Bard displayed substantial to almost perfect intra-LLM agreement (κ range, 0.65-0.86 [95% CI: 0.64, 0.86]), while ChatGPT 3.5 showed fair to substantial agreement (κ range, 0.36-0.68 [95% CI: 0.36, 0.68]). ChatGPT 4.0 had an accuracy of 78%-86% (95% CI: 76%, 88%) and sensitivity of 86%-95% (95% CI: 83%, 96%), compared with 74%-86% (95% CI: 71%, 88%) and 74%-91% (95% CI: 71%, 93%), respectively, for Bard. Moreover, with ChatGPT 4.0, the image-to-text-LLM strategy exhibited an AUC (0.83 [95% CI: 0.80, 0.85]) and accuracy (84% [95% CI: 82%, 86%]) comparable to those of the human-LLM interaction strategy with two senior readers and one junior reader and exceeding those of the human-LLM interaction strategy with one junior reader. Conclusion LLMs, particularly integrated with image-to-text approaches, show potential in enhancing diagnostic medical imaging. ChatGPT 4.0 was optimal for consistency and diagnostic accuracy when compared with Bard and ChatGPT 3.5. © RSNA, 2024 Supplemental material is available for this article.

Host-induced gene silencing in wild apple germplasm Malus hupehensis confers resistance to the fungal pathogen Botryosphaeria dothidea.

Host-induced gene silencing (HIGS) is an inherent mechanism of plant resistance to fungal pathogens, resulting from cross-kingdom RNA interference (RNAi) mediated by small RNAs (sRNAs) delivered from plants into invading fungi. Introducing artificial sRNA precursors into crops can trigger HIGS of selected fungal genes, and thus has potential applications in agricultural disease control. To investigate the HIGS of apple (Malus sp.) during the interaction with Botryosphaeria dothidea, the pathogenic fungus causing apple ring rot disease, we evaluated whether apple miRNAs can be transported into and target genes in B. dothidea. Indeed, miR159a from Malus hupehensis, a wild apple germplasm with B. dothidea resistance, silenced the fungal sugar transporter gene BdSTP. The accumulation of miR159a in extracellular vesicles (EVs) of both infected M. hupehensis and invading B. dothidea suggests that this miRNA of the host is transported into the fungus via the EV pathway. Knockout of BdSTP caused defects in fungal growth and proliferation, whereas knockin of a miR159a-insensitive version of BdSTP resulted in increased pathogenicity. Inhibition of miR159a in M. hupehensis substantially enhanced plant sensitivity to B. dothidea, indicating miR159a-mediated HIGS against BdSTP being integral to apple immunity. Introducing artificial sRNA precursors targeting BdSTP and BdALS, an acetolactate synthase gene, into M. hupehensis revealed that double-stranded RNAs were more potent than engineered MIRNAs in triggering HIGS alternative to those natural of apple and inhibiting infection. These results provide preliminary evidence for cross-kingdom RNAi in the apple-B. dothidea interaction and establish HIGS as a potential disease control strategy in apple.

The Mh-miR393a-TIR1 module regulates Alternaria alternata resistance of Malus hupehensis mainly by modulating the auxin signaling.

miRNAs govern gene expression and regulate plant defense. Alternaria alternata is a destructive fungal pathogen that damages apple. The wild apple germplasm Malus hupehensis is highly resistant to leaf spot disease caused by this fungus. Herein, we elucidated the regulatory and functional role of miR393a in apple resistance against A. alternata by targeting Transport Inhibitor Response 1. Mature miR393 accumulation in infected M. hupehensis increased owing to the transcriptional activation of MIR393a, determined to be a positive regulator of A. alternata resistance to either 'Orin' calli or 'Gala' leaves. 5' RLM-RACE and co-transformation assays showed that the target of miR393a was MhTIR1, a gene encoding a putative F-box auxin receptor that compromised apple immunity. RNA-seq analysis of transgenic calli revealed that MhTIR1 upregulated auxin signaling gene transcript levels and influenced phytohormone pathways and plant-pathogen interactions. miR393a compromised the sensitivity of several auxin-signaling genes to A. alternata infection, whereas MhTIR1 had the opposite effect. Using exogenous indole-3-acetic acid or the auxin synthesis inhibitor L-AOPP, we clarified that auxin enhances apple susceptibility to this pathogen. miR393a promotes SA biosynthesis and impedes pathogen-triggered ROS bursts by repressing TIR1-mediated auxin signaling. We uncovered the mechanism underlying the miR393a-TIR1 module, which interferes with apple defense against A. alternata by modulating the auxin signaling pathway.

Disruption of MerTK increases the efficacy of checkpoint inhibitor by enhancing ferroptosis and immune response in hepatocellular carcinoma.

Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockades, have been approved for unresectable hepatocellular carcinoma (HCC). However, high resistance rates still limit their efficacy, highlighting the urgent need to understand the underlying mechanisms and develop strategies for overcoming the resistance. In this study, we demonstrate that HCC with high MER proto-oncogene tyrosine kinase (MerTK) expression exhibits anti-PD-1/PD-L1 resistance in two syngeneic mouse models and in patients who received anti-PD-1/PD-L1 therapy. Mechanistically, MerTK renders HCC resistant to anti-PD-1/PD-L1 by limiting ferroptosis with the upregulation of SLC7A11 via the ERK/SP1 pathway and facilitating the development of an immunosuppressive tumor microenvironment (TME) with the recruitment of myeloid-derived suppressor cells (MDSCs). Sitravatinib, an inhibitor of MerTK, sensitizes resistant HCC to anti-PD-L1 therapy by promoting tumor ferroptosis and decreasing MDSC infiltration into the TME. In conclusion, we find that MerTK could serve as a predictive biomarker for patient stratification and as a promising target to overcome anti-PD-1/PD-L1 resistance in HCC.

Downregulation of Gadd45ß alleviates osteoarthritis by repressing lipopolysaccharide-induced fibroblast-like synoviocyte inflammation, proliferation and migration.

OBJECTIVE: Gadd45ß have a regulatory role in cellular inflammation, proliferation and migration. However, the role of Gadd45ß in synovial inflammation in osteoarthritis (OA) remains to be explored. This study aimed to ascertain whether Gadd45ß is involved in OA synovial inflammation. METHODS: The rat model was induced by sodium iodoacetate and the cellular model was constructed with lipopolysaccharide (LPS)-induced fibroblast-like synoviocytes (FLSs). siRNA was applied to interfere with the expression of intracellular Gadd45ß. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of Gadd45ß mRNA and protein. The inflammation, proliferation, and migration of OA-FLSs were detected by enzyme-linked immunosorbent assay, cell scratch assay, 5-ethynyl-2'-deoxyuridine assay, etc. The effect of downregulation of Gadd45ß on the nuclear factor-κB (NF-κB) pathway was investigated. RESULTS: Expression of Gadd45ß in OA rat synovial tissues and OA-FLSs was increased, and LPS treatment promoted cell proliferation and enhanced cell migration. Gadd45ß interference inhibited the inflammation, proliferation and migration of cells induced by LPS. LPS promoted P65 expression in the nucleus and activated the NF-κB signaling pathway, whereas si-Gadd45ß reversed this situation. CONCLUSIONS: si-Gadd45ß inhibited the inflammatory response, proliferation and migration of FLSs, and activation of the NF-κB signaling pathway, which could delay the progression of OA. Hence, it may become a potential therapeutic target for OA.

Biomechanical evaluation of a novel anterior transpedicular screw-plate system for anterior cervical corpectomy and fusion (ACCF): a finite element analysis.

Background and objective: Cervical fusion with vertebral body screw (VBS)-plate systems frequently results in limited biomechanical stability. To address this issue, anterior transpedicular screw (ATPS) fixation has been developed and applied preliminarily to multilevel spinal fusion, osteoporosis, and three-column injury of the cervical spine. This study aimed to compare the biomechanical differences between unilateral ATPS (UATPS), bilateral ATPS (BATPS), and VBS fixation using finite element analysis. Materials and methods: A C6 corpectomy model was performed and a titanium mesh cage (TMC) and bone were implanted, followed by implantation of a novel ATPS-plate system into C5 and C7 to simulate internal fixation with UATPS, BATPS, and VBS. Internal fixation with UATPS comprises ipsilateral transpedicular screw-contralateral vertebral body screw (ITPS-CVBS) and cross transpedicular screw-vertebral body screw (CTPS-VBS) fixations. Mobility, the maximal von Mises stress on TMC, the stress distribution and maximal von Mises stress on the screws, and the maximum displacement of the screw were compared between the four groups. Results: Compared with the original model, each group had a reduced range of motion (ROM) under six loads. After ACCF, the stress was predominantly concentrated at two-thirds of the length from the tail of the screw, and it was higher on ATPS than on VBS. The stress of the ATPS from the cranial part was higher than that of the caudal part. The similar effect happened on VBS. The screw stress cloud maps did not show any red areas reflective of a concentration of the stress on VBS. Compared with VBS, ATPS can bear a greater stress from cervical spine movements, thus reducing the stress on TMC. The maximal von Mises stress was the lowest with bilateral transpedicular TMC and increased with cross ATPS and with ipsilateral ATPS. ITPS-CVBS, CTPS-VBS, and BATPS exhibited a reduction of 2.3%-22.1%, 11.9%-2.7%, and 37.9%-64.1% in the maximum displacement of screws, respectively, compared with that of VBS. Conclusion: In FEA, the comprehensive stability ranked highest for BATPS, followed by CTPS-VBS and ITPS-CVBS, with VBS demonstrating the lowest stability. Notably, utilizing ATPS for fixation has the potential to reduce the occurrence of internal fixation device loosening after ACCF when compared to VBS.

DDIT4 Facilitates Lymph Node Metastasis via the Activation of NF-κB Pathway and Epithelial-Mesenchymal Transition.

This study was aimed to identify a novel metastasis-promoting molecule and elucidate its functional and prognostic roles in cervical cancer. DDIT4 (DNA-damage-inducible transcript 4), a hypoxia-inducible gene, was identified by analyzing multiple microarray databases. The correlation between DDIT4 expression in immunohistochemistry and clinicopathological characteristics in the public database and our cohort was evaluated by statistical analysis. Transwell® assay and wound-healing assay to determine cell migration and invasion were performed. DDIT4 was knocked down using siRNA or lentiviral vectors. The potential downstream pathways of DDIT4 were explored and verified by a gene set enrichment analysis and western blotting. The in vivo metastatic capability was determined with the use of an intraperitoneal injection mouse model. In the analysis of the public database and our cohort, DDIT4 high expression was significantly related to short overall survival and lymph node metastasis in patients with early-stage cervical cancer. The knockdown of DDIT4 attenuated the migration and invasion activity of tumor cells in vitro and reduced the expression of epithelial-mesenchymal transition (EMT)-related proteins and the NF-κB pathway in cervical cancer cells. DDIT4 also promoted tumor progression in the mouse model. Our results indicate that DDIT4 can be a prognostic indicator in cervical cancer and promote lymph node metastasis, augmenting malignancy via the EMT and NF-kB pathways.

Effects of dysfunctional beliefs about sleep on sleep quality and mental health among patients with COVID-19 treated in Fangcang shelter hospitals.

Introduction: With the COVID-19 pandemic in China, a large number of mild or ordinary confirmed cases have been sent to Fangcang shelter hospitals for treatment. We aimed to investigate the mental health condition of Fangcang patients 2 years after the pandemic when patients knew more about COVID-19 and the virus was less virulent. We focused on the effect of dysfunctional beliefs and attitudes about sleep on depression, anxiety, and insomnia. Methods: A total of 1,014 patients from two large Fangcang shelter hospitals in Shanghai between 22 April and 8 May 2022 completed a set of questionnaires comprising: the Dysfunctional Beliefs and Attitudes about Sleep scale, the Generalized Anxiety Disorder scale, the Patient Health Questionnaire, and the Insomnia Severity Index scale. Results: Results show that the positive screening rates for anxiety, depression, and insomnia among tested patients were 55.3, 27.0, and 47.8%, respectively. Patients were more likely to report higher anxiety, depression, and insomnia, and to endorse affective and sleep disorders if they were: female, aged 18-40 years, with undergraduate course or above, white-collar employees, or those who thought the pandemic would have severe economic effects. About 51.4% of the participants had dysfunctional beliefs about sleep to varying degrees. Compared with patients who had accurate beliefs about sleep, the ratios of insomnia, anxiety, and depression were significantly higher among patients with dysfunctional beliefs about sleep. Discussion: Attention should be paid to the mental health problems of patients in Fangcang shelter hospitals. The results indicate that dysfunctional beliefs about sleep significantly increased anxiety, depression, and insomnia of Fangcang patients.

Questionnaires based on natural language processing elicit immersive ruminative thinking in ruminators: Evidence from behavioral responses and EEG data.

Rumination is closely related to mental disorders and can thus be used as a marker of their presence or a predictor of their development. The presence of masking and fabrication in psychological selection can lead to inaccurate detection of psychological disorders. Human language is considered crucial in eliciting specific conscious activities, and the use of natural language processing (NLP) in the development of questionnaires for psychological tests has the potential to elicit immersive ruminative thinking, leading to changes in neural activity. Electroencephalography (EEG) is commonly used to detect and record neural activity in the human brain and is sensitive to changes in brain activity. In this study, we used NLP to develop a questionnaire to induce ruminative thinking and then recorded the EEG signals in response to the questionnaire. The behavioral results revealed that ruminators exhibited higher arousal rates and longer reaction times, specifically in response to the ruminative items of the questionnaire. The EEG results showed no significant difference between the ruminators and the control group during the resting state; however, a significant alteration in the coherence of the entire brain of the ruminators existed while they were answering the ruminative items. No differences were found in the control participants while answering the two items. These behavioral and EEG results indicate that the questionnaire elicited immersive ruminative thinking, specifically in the ruminators. Therefore, the questionnaire designed using NLP is capable of eliciting ruminative thinking in ruminators, offering a promising approach for the early detection of mental disorders in psychological selection.

Electrophysiological Mechanism of Attention of Sleep Deprivation: Evidence From Event-Related Potentials (ERP) Data.

INTRODUCTION: The purpose of this study is to investigate the effects of sleep deprivation on individual attentional function and related electrophysiological mechanisms. METHODS: Twenty healthy men who were deprived of sleep for 24 h were evaluated by selective attention test, persistent attention test, and event-related potentials (ERP) experiment. RESULTS: After 24 h of sleep deprivation, the subjects' selective attention decreased, mainly manifested as prolonged response time, decreased motion stability, increased rate of neglect error, decreased sustained attention, prolonged latency of P300 at Cz (p=0.001), and decreased amplitude (p=0.000). CONCLUSION: After 24 h of sleep deprivation, the attentional ability decreased significantly, and behavioral and ERP indicators showed certain changes.

DeepFundus: A flow-cytometry-like image quality classifier for boosting the whole life cycle of medical artificial intelligence.

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.

Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies.

Hydrogen sulfide (H2S) is an important signaling molecule in colorectal cancer (CRC). It is produced in the colon by the catalytic synthesis of the colonocytes' enzymatic systems and the release of intestinal microbes, and is oxidatively metabolized in the colonocytes' mitochondria. Both endogenous H2S in colonic epithelial cells and exogenous H2S in intestinal lumen contribute to the onset and progression of CRC. The up-regulation of endogenous synthetases is thought to be the cause of the elevated H2S levels in CRC cells. Different diagnostic probes and combination therapies, as well as tumor treatment approaches through H2S modulation, have been developed in recent years and have become active area of investigation for the diagnosis and treatment of CRC. In this review, we focus on the specific mechanisms of H2S production and oxidative metabolism as well as the function of H2S in the occurrence, progression, diagnosis, and treatment of CRC. We also discuss the present challenges and provide insights into the future research of this burgeoning field.