Calcium transients on the ER surface trigger liquid-liquid phase separation of FIP200 to specify autophagosome initiation sites.

The mechanism that initiates autophagosome formation on the ER in multicellular organisms is elusive. Here, we showed that autophagy stimuli trigger Ca2+ transients on the outer surface of the ER membrane, whose amplitude, frequency, and duration are controlled by the metazoan-specific ER transmembrane autophagy protein EPG-4/EI24. Persistent Ca2+ transients/oscillations on the cytosolic ER surface in EI24-depleted cells cause accumulation of FIP200 autophagosome initiation complexes on the ER. This defect is suppressed by attenuating ER Ca2+ transients. Multi-modal SIM analysis revealed that Ca2+ transients on the ER trigger the formation of dynamic and fusion-prone liquid-like FIP200 puncta. Starvation-induced Ca2+ transients on lysosomes also induce FIP200 puncta that further move to the ER. Multiple FIP200 puncta on the ER, whose association depends on the ER proteins VAPA/B and ATL2/3, assemble into autophagosome formation sites. Thus, Ca2+ transients are crucial for triggering phase separation of FIP200 to specify autophagosome initiation sites in metazoans.

Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion.

DNA-induced liquid-liquid phase separation of cyclic GMP-AMP synthase (cGAS) triggers a potent response to detect pathogen infection and promote innate immune signaling. Whether and how pathogens manipulate cGAS-DNA condensation to mediate immune evasion is unknown. We report the identification of a structurally related viral tegument protein family, represented by ORF52 and VP22 from gamma- and alpha-herpesvirinae, respectively, that employs a conserved mechanism to restrict cGAS-DNA phase separation. ORF52/VP22 proteins accumulate into, and effectively disrupt, the pre-formed cGAS-DNA condensation both in vitro and in cells. The inhibition process is dependent on DNA-induced liquid-liquid phase separation of the viral protein rather than a direct interaction with cGAS. Moreover, highly abundant ORF52 proteins carried within viral particles are able to target cGAS-DNA phase separation in early infection stage. Our results define ORF52/VP22-type tegument proteins as a family of inhibitors targeting cGAS-DNA phase separation and demonstrate a mechanism for how viruses overcome innate immunity.

3D reconstruction and multi-omics analysis reveal a unique pattern of embryogenesis in Ginkgo biloba.

Ginkgo (Ginkgo biloba L.) is one of the earliest extant species in seed plant phylogeny. Embryo development patterns can provide fundamental evidence for the origin, evolution, and adaptation of seeds. However, the architectural and morphological dynamics during embryogenesis in Ginkgo biloba (G. biloba) remain elusive. Herein, we obtained over 2200 visual slices from three stages of embryo development using micro-computed tomography imaging with improved staining methods. Based on 3D spatio-temporal pattern analysis, we found that a shoot apical meristem with seven highly differentiated leaf primordia, including apical and axillary leaf buds, is present in mature Ginkgo embryos. 3D rendering from the front, top, and side views showed two separate transport systems of tracheids located in the hypocotyl and cotyledon, representing a unique pattern of embryogenesis. Furthermore, the morphological dynamic analysis of secretory cavities indicated their strong association with cotyledons during development. In addition, we identified genes GbLBD25a (lateral organ boundaries domain 25a), GbCESA2a (cellulose synthase 2a), GbMYB74c (myeloblastosis 74c), GbPIN2 (PIN-FORMED 2) associated with vascular development regulation, and GbWRKY1 (WRKYGOK 1), GbbHLH12a (basic helix-loop-helix 12a), GbJAZ4 (jasmonate zim-domain 4) potentially involved in the formation of secretory cavities. Moreover, we found that flavonoid accumulation in mature embryos could enhance post-germinative growth and seedling establishment in harsh environments. Our 3D spatial reconstruction technique combined with multi-omics analysis opens avenues for investigating developmental architecture and molecular mechanisms during embryogenesis and lays the foundation for evolutionary studies of embryo development and maturation.

Metal-Organic Framework-Based Surface-Enhanced Raman Scattering Sensing Platform for Trace Malondialdehyde Detection in Tears.

Disease biomarkers in tears are crucial for clinical diagnosis and health monitoring. However, the limited volume of tear samples, low concentration of tear biomarkers, and complex tear composition present challenges for precise testing. We introduce a spot-on testing platform of metal-organic framework (MOF)-based surface-enhanced Raman scattering (SERS) capillary column, which is capable of target molecules selective separation and enrichment for tear biomarkers in situ detection. It consists of Au nanostars for effective SERS signal and a porous MOF shell for separating impurities through molecular sieving effect. This platform allows for simultaneous collection and detection of tear, capturing the disease biomarker malondialdehyde in tears with a 9.38 × 10-9 mol/L limit of detection. Moreover, we designed a hand-held device based on this tubular SERS sensor, successfully diagnosing patients with dry eye disease. This functional capillary column enables noninvasive and rapid diagnosis of biomarkers in biofluids, providing potential for disease diagnosis and healthcare monitoring.

Boosting the ORR/OER Activity of Cobalt-Based Nano-Catalysts by Co 3d Orbital Regulation.

The transition metal oxides/sulfides are considered promising catalysts due to their abundant resources, facile synthesis, and reasonable electrocatalytic activity. Herein, a significantly improved intrinsic catalytic activity is achieved for constructing a Co-based nanocrystal (Co-S@NC) with the coordination of Co─S, Co─S─C, and Co─Nx─C. The calculational and experimental results demonstrate that the diversified chemical environment of Co-cations induces the transition of 3d orbitals to a high spin-state that exhibits the coexistence of Co2+ with fully occupied dπ orbitals and Co3+ with unpaired electrons in dπ orbitals. The diverse dπ orbitals occupation contributes to an elevated d-band center of Co ions, which accelerates oxygen reduction reaction and oxygen evolution reaction electrocatalytic kinetics of the Co-S@NC nanocrystal. Therefore, the Li-O2 batteries with Co-S@NC as cathode catalyst exhibit 300 cycles at the current density of 500 mA g-1 with a cut-off capacity of 1000 mAh g-1. Moreover, the ultrahigh discharge specific capacity of 34 587 mAh g-1 is obtained at a current density of 1000 mA g-1, corresponding to the energy density 949 Wh kg-1 of a prototype Li-O2 battery. The study on 3d orbital regulation of nanocrystals provides an innovative strategy for bifunctional electrocatalysts toward the practical application of metal-air batteries.

The Arabidopsis histone demethylase JMJ28 regulates CONSTANS by interacting with FBH transcription factors.

Arabidopsis thaliana CONSTANS (CO) is an essential transcription factor that promotes flowering by activating the expression of the floral integrator FLOWERING LOCUS T (FT). A number of histone modification enzymes involved in the regulation of flowering have been identified, but the involvement of epigenetic mechanisms in the regulation of the core flowering regulator CO remains unclear. Previous studies have indicated that the transcription factors, FLOWERING BHLH1 (FBH1), FBH2, FBH3, and FBH4, function redundantly to activate the expression of CO. In this study, we found that the KDM3 group H3K9 demethylase JMJ28 interacts with the FBH transcription factors to activate CO by removing the repressive mark H3K9me2. The occupancy of JMJ28 on the CO locus is decreased in the fbh quadruple mutant, suggesting that the binding of JMJ28 is dependent on FBHs. Furthermore, genome-wide occupancy profile analyses indicate that the binding of JMJ28 to the genome overlaps with that of FBH3, indicating a functional association of JMJ28 and FBH3. Together, these results indicate that Arabidopsis JMJ28 functions as a CO activator by interacting with the FBH transcription factors to remove H3K9me2 from the CO locus.

Deciphering the molecular symphony: Unraveling endothelial-to-mesenchymal transition in corneal endothelial cells.

Understanding the molecular complexity of this phenomenon provides innovative targets for maintaining phenotypic integrity during in vitro expansion, thereby advancing corneal endothelial tissue engineering. In this study, we established an in vitro model to simulate endothelial-to-mesenchymal transition (EndMT) in corneal endothelial cells. Through RNA sequencing, we identified 452 upregulated and 163 downregulated genes, resulting in a total of 615 differentially expressed genes. Key pathways enriched by GO and KEGG analysis include extracellular matrix (ECM) regulation and the PI3K-Akt signaling pathway. Potential hub proteins such as THBS1, ITGA5, COL1A1, and SNAI1/2 were also identified, and their dynamic changes at different time points (0, 2, 12, 24 h) were monitored. Uncovering these key pathways and genes may deepen our understanding of the mechanisms underlying EndMT in corneal endothelial cells, providing valuable insights for optimizing in vitro cultivation strategies.

Risk Factors Analysis of Severe Liver Injury Induced by Statins.

The aim of this study is to report the risk factors of severe statin induced liver injury (SILI). From the database of Shandong ADR Monitoring Center and Outpatients and inpatients in our hospital, SILI cases reported from 2013 to 2021 were extracted and screened. The diagnostic criteria of SILI, the inclusion and exclusion criteria of severe and general SILI were established separately. After the SILI cases were selected and confirmed, the socio-demographic and clinical characteristics were collected. Single factor chi-square test and multi-factor unconditional logistic regression analysis were used to analyze the influencing factors of severe SILI. From 1391 reported cases, 1211 met SILI diagnostic criteria, of which 157 were severe SILI and 964 were general SILI. Univariate analysis showed that age, drug combination, statin category were the influencing factors of severe SILI (p<0.1). Multivariate logistic analysis showed that drug combination and statin category were the influencing factors of severe SILI (p<0.05). Atorvastatin caused the most serious SILI, and its risk is 1.77 times higher than rosuvastatin. The serious SILI risk of drug combination was 2.08 times higher than statin alone. The patient with these factors should be monitored intensively during clinical treatment, to ensure their medication safety.

The association between Helicobacter pylori and gastrointestinal disorders during pregnancy: A Multicenter retrospective study.

BACKGROUND: Some gastrointestinal disorders may be associated with Helicobacter pylori infection, which not only affect maternal health, but may also lead to adverse pregnancy outcomes. We aim to explore the association between H. pylori and gastrointestinal disorders in pregnant women. MATERIALS AND METHODS: In total, 503 patients were retrospectively analyzed and divided into the H. pylori-uninfected group, the H. pylori-infected group, or the H. pylori-eradicated group. We analyzed the influence of H. pylori on gastrointestinal diseases during pregnancy among the groups, as well as the severity, symptoms, laboratory tests of the H. pylori-related diseases. RESULTS: Pregnant women with H. pylori infection had higher risk of nausea and vomiting of pregnancy (NVP) (p < 0.001), severe NVP(p = 0.012), hyperemesis gravidarum (p = 0.027), hematemesis (p = 0.018), hyponatremia (p = 0.033), as well as functional dyspepsia symptoms including epigastric pain (p = 0.004), bloating (p = 0.024), and feeling full quickly in a meal (p = 0.031) compared with those without H. pylori infection. While the prevalence of NVP (p = 0.024), severe NVP (p = 0.009), epigastric pain (p = 0.037), and bloating (p = 0.032) were lower in H. pylori-eradicated pregnant women than in H. pylori-infected women. In addition, pregnant women with H. pylori infection had higher risk of spontaneous preterm birth than whom without H. pylori infection (p = 0.033). CONCLUSIONS: Helicobacter pylori infection was associated with higher risks of NVP, severe NVP, hyperemesis gravidarum, functional dyspepsia, and spontaneous preterm birth in pregnant women.

Persistence of T Cell and Antibody Responses to SARS-CoV-2 Up to 9 Months after Symptom Onset.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces T cell, B cell, and Ab responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. In this study, we followed T cell and Ab responses in 24 mainly nonhospitalized human subjects who had recovered from PCR-confirmed SARS-CoV-2 infection at two time points (median of 45 and 145 d after symptom onset). Ab responses were detected in 95% of subjects, with a strong correlation between plasma and salivary anti-spike (anti-S) and anti-receptor binding domain IgG, as well as a correlation between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response. T cell responses to SARS-CoV-2 peptides were determined using intracellular cytokine staining, activation markers, proliferation, and cytokine secretion. All study subjects had a T cell response to at least one SARS-CoV-2 Ag based on at least one T cell assay. CD4+ responses were largely of the Th1 phenotype, but with a lower ratio of IFN-γ- to IL-2-producing cells and a lower frequency of CD8+:CD4+ T cells than in influenza A virus (IAV)-specific memory responses within the same subjects. Analysis of secreted molecules also revealed a lower ratio of IFN-γ to IL-2 and an altered cytotoxic profile for SARS-CoV-2 S- and nucleocapsid-specific responses compared with IAV-specific responses. These data suggest that the memory T cell phenotype after a single infection with SARS-CoV-2 persists over time, with an altered cytokine and cytotoxicity profile compared with long-term memory to whole IAV within the same subjects.

Expression of regional brain amyloid-ß deposition with [18F]Flutemetamol in Centiloid scale -a multi-site study.

PURPOSE: The Centiloid project helps calibrate the quantitative amyloid-ß (Aß) load into a unified Centiloid (CL) scale that allows data comparison across multi-site. How the smaller regional amyloid converted into CL has not been attempted. We first aimed to express regional Aß deposition in CL using [18F]Flutemetamol and evaluate regional Aß deposition in CL with that in standardized uptake value ratio (SUVr). Second, we aimed to determine the presence or absence of focal Aß deposition by measuring regional CL in equivocal cases showing negative global CL. METHODS: Following the Centiloid project pipeline, Level-1 replication, Level-2 calibration, and quality control were completed to generate corresponding Centiloid conversion equations to convert SUVr into Centiloid at regional levels. In equivocal cases, the regional CL was compared with visual inspection to evaluate regional Aß positivity. RESULTS: 14 out of 16 regional conversions from [18F]Flutemetamol SUVr to Centiloid successfully passed the quality control, showing good reliability and relative variance, especially precuneus/posterior cingulate and prefrontal regions with good stability for Centiloid scaling. The absence of focal Aß deposition could be detected by measuring regional CL, showing a high agreement rate with visual inspection. The regional Aß positivity in the bilateral anterior cingulate cortex was most prevalent in equivocal cases. CONCLUSION: The expression of regional brain Aß deposition in CL with [18F]Flutemetamol has been attempted in this study. Equivocal cases had focal Aß deposition that can be detected by measuring regional CL.

Improving the production of carbamoyltobramycin by an industrial Streptoalloteichus tenebrarius through metabolic engineering.

Tobramycin is an essential and extensively used broad-spectrum aminoglycoside antibiotic obtained through alkaline hydrolysis of carbamoyltobramycin, one of the fermentation products of Streptoalloteichus tenebrarius. To simplify the composition of fermentation products from industrial strain, the main byproduct apramycin was blocked by gene disruption and constructed a mutant mainly producing carbamoyltobramycin. The generation of antibiotics is significantly affected by the secondary metabolism of actinomycetes which could be controlled by modifying the pathway-specific regulatory proteins within the cluster. Within the tobramycin biosynthesis cluster, a transcriptional regulatory factor TobR belonging to the Lrp/AsnC family was identified. Based on the sequence and structural characteristics, tobR might encode a pathway-specific transcriptional regulatory factor during biosynthesis. Knockout and overexpression strains of tobR were constructed to investigate its role in carbamoyltobramycin production. Results showed that knockout of TobR increased carbamoyltobramycin biosynthesis by 22.35%, whereas its overexpression decreased carbamoyltobramycin production by 10.23%. In vitro electrophoretic mobility shift assay (EMSA) experiments confirmed that TobR interacts with DNA at the adjacent tobO promoter position. Strains overexpressing tobO with ermEp* promoter exhibited 36.36% increase, and tobO with kasOp* promoter exhibited 22.84% increase in carbamoyltobramycin titer. When the overexpressing of tobO and the knockout of tobR were combined, the production of carbamoyltobramycin was further enhanced. In the shake-flask fermentation, the titer reached 3.76 g/L, which was 42.42% higher than that of starting strain. Understanding the role of Lrp/AsnC family transcription regulators would be useful for other antibiotic biosynthesis in other actinomycetes. KEY POINTS: • The transcriptional regulator TobR belonging to the Lrp/AsnC family was identified.  • An oxygenase TobO was identified within the tobramycin biosynthesis cluster. • TobO and TobR have significant effects on the synthesis of carbamoyltobramycin.

Discrimination between benign and malignant gallbladder lesions on enhanced CT imaging using radiomics.

BACKGROUND: Gallbladder cancer is a rare but aggressive malignancy that is often diagnosed at an advanced stage and is associated with poor outcomes. PURPOSE: To develop a radiomics model to discriminate between benign and malignant gallbladder lesions using enhanced computed tomography (CT) imaging. MATERIAL AND METHODS: All patients had a preoperative contrast-enhanced CT scan, which was independently analyzed by two radiologists. Regions of interest were manually delineated on portal venous phase images, and radiomics features were extracted. Feature selection was performed using mRMR and LASSO methods. The patients were randomly divided into training and test groups at a ratio of 7:3. Clinical and radiomics parameters were identified in the training group, three models were constructed, and the models' prediction accuracy and ability were evaluated using AUC and calibration curves. RESULTS: In the training group, the AUCs of the clinical model and radiomics model were 0.914 and 0.968, and that of the nomogram model was 0.980, respectively. There were statistically significant differences in diagnostic accuracy between nomograms and radiomics features (P <0.05). There was no significant difference in diagnostic accuracy between the nomograms and clinical features (P >0.05) or between the clinical features and radiomics features (P >0.05). In the testing group, the AUC of the clinical model and radiomics model were 0.904 and 0.941, and that of the nomogram model was 0.948, respectively. There was no significant difference in diagnostic accuracy between the three groups (P >0.05). CONCLUSION: It was suggested that radiomics analysis using enhanced CT imaging can effectively discriminate between benign and malignant gallbladder lesions.

Improving intracranial aneurysms image quality and diagnostic confidence with deep learning reconstruction in craniocervical CT angiography.

BACKGROUND: The diagnostic impact of deep learning computed tomography (CT) reconstruction on intracranial aneurysm (IA) remains unclear. PURPOSE: To quantify the image quality and diagnostic confidence on IA in craniocervical CT angiography (CTA) reconstructed with DEep Learning Trained Algorithm (DELTA) compared to the routine hybrid iterative reconstruction (HIR). MATERIAL AND METHODS: A total of 60 patients who underwent craniocervical CTA and were diagnosed with IA were retrospectively enrolled. Images were reconstructed with DELTA and HIR, where the image quality was first compared in noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Next, two radiologists independently graded the noise appearance, arterial sharpness, small vessel visibility, conspicuity of calcifications that may present in arteries, and overall image quality, each with a 5-point Likert scale. The diagnostic confidence on IAs of various sizes was also graded. RESULTS: Significantly lower noise and higher SNR and CNR were found on DELTA than on HIR images (all P < 0.05). All five subjective metrics were scored higher by both readers on the DELTA images (all P < 0.05), with good to excellent inter-observer agreement (κ = 0.77-0.93). DELTA images were rated with higher diagnostic confidence on IAs compared to HIR (P < 0.001), particularly for those with size ≤3 mm, which were scored 4.5 ± 0.6 versus 3.4 ± 0.8 and 4.4 ± 0.7 versus 3.5 ± 0.8 by two readers, respectively. CONCLUSION: The DELTA shows potential for improving the image quality and the associated confidence in diagnosing IA that may be worth consideration for routine craniocervical CTA applications.

Low muscle density in children with osteogenesis imperfecta using opportunistic low-dose chest CT: a case-control study.

BACKGROUND: The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children. METHODS: This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests. RESULTS: 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p < 0.01; 37.3 HU vs. 45.9 HU, p < 0.01). However, children with OI had lower T4 muscle size, T4 muscle density, T10 muscle size and T10 muscle density than controls measured by the Gaussian mixture model (110.9 vs. 127.2 cm2, p = 0.03; 44.6 HU vs. 51.3 HU, p < 0.01; 72.6 vs. 88.0 cm2, p = 0.01; 41.6 HU vs. 50.3 HU, p < 0.01, respectively). CONCLUSIONS: Children with OI had lower trunk muscle density indicating that OI might also impair muscle quality. Moreover, the fixed thresholds may not be suitable for segmentation of muscle in children.

Comparison of Easydo Activator, ultrasonic and needle irrigation techniques on sealer penetration and smear layer removal in vitro.

The effects of Easydo Activator (EA), a new sonic irrigation system, on sealer penetration at the root apex were compared to needle irrigation (NI) and passive ultrasonic irrigation (PUI) in this study. Forty-two single-rooted teeth were prepared and randomly divided into three groups (n = 14): group 1: NI; group 2: PUI; and group 3: EA. A solution of 3% sodium hypochlorite (NaOCl) was used for irrigation. Nine teeth in each group were filled with AH Plus sealer mixed with CY5 fluorescent dye and a single gutta-percha cone. The sealer penetration area, maximum penetration depth and percentage of sealer penetration at 5 mm and 1 mm from the apex were analyzed by confocal laser scanning microscopy (CLSM). The remaining 5 teeth in each group were subjected to test smear layer scores by scanning electron microscopy (SEM). The CLSM evaluation showed that increases in the area, depth and percentage of sealer penetration were detected at 1 and 5 mm from the root apex in the PUI group compared with the NI group, and greater increases were observed in the EA group (P < 0.05). The SEM experiment showed that the lowest scores for the smear layer and debris removal were achieved by the EA group when compared with the PUI and NI groups (P < 0.05). In conclusion, EA was superior to PUI and NI regarding sealer penetration at the root apex during endodontic treatment, and it could provide a new technical idea for clinical root canal therapy.

[A new nor-neolignan compound identified from Itea yunnanensis].

Various separation methods in combination with spectral data analysis, X-ray single crystal diffraction analysis, and litera-ture data comparison were employed to clarify the chemical constituents of Itea yunnanensis. Seven compounds were obtained from I. yunnanensis, which were identified as(S)-3-[1-(4-hydroxyphenyl)propane-2-yl]-4-methoxybenzoate methyl ester(1), iteafuranal B(2), syringaresinol(3), dihydrokaempferol(4), trimethoxybenzene(5), eicosane(6), and nonacosane(7), respectively. Among them, compound 1 was a new nor-neolignan compound named iteanorneoligan A, and the rest of the compounds were identified from I. yunnanensis for the first time. The anti-hepatocellular carcinoma effect of the compound was evaluated based on Sk-hep-1 cells model via MTT assay, and compound 2 showed a significant inhibitory effect on the proliferation of Sk-hep-1 cells with an IC_(50) of 9.4 µmol·L~(-1). The antioxidant capacity was determined via DPPH, ABTS~(·+), and O■ radical scavenging ability, and compound 1 exhibited a significant ABTS~(·+) radical scavenging effect with an IC_(50) of 0.178 mg·mL~(-1).

[Clinical study of prone positioning in invasive respiratory support for neonatal respiratory distress syndrome]. / ä¿¯å§ä½åœ¨æ–°ç”Ÿå„¿å‘¼å¸çª˜è¿«ç»¼åˆå¾æœ‰åˆ›å‘¼å¸æ”¯æŒä¸­çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome (NRDS) using invasive respiratory support. METHODS: A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital, involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS. The infants were randomly divided into a supine group (37 infants) and a prone group (40 infants). Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position, continuing in this cycle until weaning from the ventilator. The effectiveness and safety of the two approaches were compared. RESULTS: At 6 hours after enrollment, the prone group showed lower arterial blood carbon dioxide levels, inspired oxygen concentration, oxygenation index, rates of tracheal intubation bacterial colonization, and Neonatal Pain, Agitation and Sedation Scale scores compared to the supine group (P<0.05). There were no significant differences between the groups in terms of pH, arterial oxygen pressure, positive end-expiratory pressure, duration of mechanical ventilation, accidental extubation, ventilator-associated pneumonia, air leak syndrome, skin pressure sores, feeding intolerance, and grades II-IV intraventricular hemorrhage (P>0.05). CONCLUSIONS: Compared to supine positioning, prone ventilation effectively improves oxygenation, increases comfort, and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS, without significantly increasing adverse reactions.

A gene mutation-based risk model for prognostic prediction in liver metastases.

BACKGROUND: Liver metastasis is the major challenge in the treatment for malignant tumors. Genomic profiling is increasingly used in the diagnosis, treatment and prediction of prognosis in malignancies. In this study, we constructed a gene mutation-based risk model to predict the survival of liver metastases. METHOD: We identified the gene mutations associated with survival and constructed the risk model in the training cohort including 800 patients with liver metastases from Memorial Sloan-Kettering Cancer Center (MSKCC) dataset. Other 794 patients with liver metastases were collected from 4 cohorts for validation. Furthermore, the analyses of tumor microenvironment (TME) and somatic mutations were performed on 51 patients with breast cancer liver metastases (BCLM) who had both somatic mutation data and RNA-sequencing data. RESULTS: A gene mutation-based risk model involved 10 genes was constructed to divide patients with liver metastases into the high- and low-risk groups. Patients in the low-risk group had a longer survival time compared to those in the high-risk group, which was observed in both training and validation cohorts. The analyses of TME in BCLM showed that the low-risk group exhibited more immune infiltration than the high-risk group. Furthermore, the mutation signatures of the high-risk group were completely different from those of the low-risk group in patients with BCLM. CONCLUSIONS: The gene mutation-based risk model constructed in our study exhibited the reliable ability of predicting the prognosis in liver metastases. The difference of TME and somatic mutations among BCLM patients with different risk score can guide the further research and treatment decisions for liver metastases.

A Coronary CT Angiography Radiomics Model to Identify Vulnerable Plaque and Predict Cardiovascular Events.

Background A noninvasive coronary CT angiography (CCTA)-based radiomics technique may facilitate the identification of vulnerable plaques and patients at risk for future adverse events. Purpose To assess whether a CCTA-based radiomic signature (RS) of vulnerable plaques defined with intravascular US was associated with increased risk for future major adverse cardiac events (MACE). Materials and Methods In a retrospective study, an RS of vulnerable plaques was developed and validated using intravascular US as the reference standard. The RS development data set included patients first undergoing CCTA and then intravascular US within 3 months between June 2013 and December 2020 at one tertiary hospital. The development set was randomly assigned to training and validation sets at a 7:3 ratio. Diagnostic performance was assessed internally and externally from three tertiary hospitals using the area under the curve (AUC). The prognostic value of the RS for predicting MACE was evaluated in a prospective cohort with suspected coronary artery disease between April 2018 and March 2019. Multivariable Cox regression analysis was used to evaluate the RS and conventional anatomic plaque features (eg, segment involvement score) for predicting MACE. Results The RS development data set included 419 lesions from 225 patients (mean age, 64 years ± 10 [SD]; 68 men), while the prognostic cohort included 1020 lesions from 708 patients (mean age, 62 years ± 11; 498 men). Sixteen radiomic features, including two shape features and 14 textural features, were selected to build the RS. The RS yielded a moderate to good AUC in the training, validation, internal, and external test sets (AUC = 0.81, 0.75, 0.80, and 0.77, respectively). A high RS (≥1.07) was independently associated with MACE over a median 3-year follow-up (hazard ratio, 2.01; P = .005). Conclusion A coronary CT angiography-derived radiomic signature of coronary plaque enabled the detection of vulnerable plaques that were associated with increased risk for future adverse cardiac outcomes. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by De Cecco and van Assen in this issue.