US-based Sequential Algorithm Integrating an AI Model for Advanced Liver Fibrosis Screening.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities. A US-based DL network (FIB-Net) was trained on US images to predict whether the shear-wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis-4 Index (FIB-4) followed by FIB-Net and a three-step algorithm (Three-step#1) using FIB-4 followed by FIB-Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB-4, SWE, FIB-Net, and European Association for the Study of the Liver guidelines (ie, FIB-4 followed by SWE), along with sequential algorithms. Results The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB-Net obtained a noninferior specificity with a margin of 5% (P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB-4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion A sequential algorithm combining FIB-4 and a US DL model showed higher diagnostic accuracy and improved referral management for all-cause advanced liver fibrosis compared with FIB-4 or the DL model alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ghosh in this issue.

Predictive value of intraoperative contrast-enhanced ultrasound in functional recovery of non-traumatic cervical spinal cord injury.

OBJECTIVES: To evaluate the ability of intraoperative CEUS to predict neurological recovery in patients with degenerative cervical myelopathy (DCM). METHODS: Twenty-six patients with DCM who underwent laminoplasty and intraoperative ultrasound (IOUS) were included in this prospective study. The modified Japanese Orthopaedic Association (mJOA) scores and MRI were assessed before surgery and 12 months postoperatively. The anteroposterior diameter (APD), maximum spinal cord compression (MSCC), and area of signal changes in the cord at the compressed and normal levels were measured and compared using MRI and IOUS. Conventional blood flow and CEUS indices (time to peak, ascending slope, peak intensity (PI), and area under the curve (AUC)) at different levels during IOUS were calculated and analysed. Correlations between all indicators and the neurological recovery rate were evaluated. RESULTS: All patients underwent IOUS and intraoperative CEUS, and the total recovery rate was 50.7 ± 33.3%. APD and MSCC improved significantly (p < 0.01). The recovery rate of the hyperechoic lesion group was significantly worse than that of the isoechoic group (p = 0.016). 22 patients were analysed by contrast analysis software. PI was higher in the compressed zone than in the normal zone (24.58 ± 3.19 versus 22.43 ± 2.39, p = 0.019). ΔPI compress-normal and ΔAUC compress-normal of the hyperechoic lesion group were significantly higher than those of the isoechoic group (median 2.19 versus 0.55, p = 0.017; 135.7 versus 21.54, p = 0.014, respectively), and both indices were moderately negatively correlated with the recovery rate (r = - 0.463, p = 0.030; r = - 0.466, p = 0.029). CONCLUSIONS: Signal changes and microvascular perfusion evaluated using CEUS during surgery are valuable predictors of cervical myelopathy prognosis. CLINICAL RELEVANCE STATEMENT: In the spinal cord compression area of degenerative cervical myelopathy, especially in the hyperechoic lesions, intraoperative CEUS showed more significant contrast agent perfusion than in the normal area, and the degree was negatively correlated with the neurological prognosis. KEY POINTS: • Recovery rates in patients with hyperechoic findings were lower than those of patients without lesions detected during intraoperative ultrasound. • The peak intensity of CEUS was higher in compressed zones than in the normal parts of the spinal cord. • Quantitative CEUS comparisons of the peak intensity and area under the curve at the compressed and normal levels of the spinal cord revealed differences that were inversely correlated to the recovery rate.

Preliminarily exploring the intraoperative ultrasonography characteristics of patients with degenerative cervical myelopathy.

BACKGROUND: How to quickly read and interpret intraoperative ultrasound (IOUS) images of patients with degenerative cervical myelopathy (DCM) to obtain meaningful information? Few studies have systematically explored this topic. PURPOSE: To systematically and comprehensively explore the IOUS characteristics of patients with DCM. MATERIALS AND METHODS: This single-center study retrospectively included patients with DCM who underwent French-door laminoplasty (FDL) with IOUS guidance from October 2019 to March 2022. One-way ANOVA and Pearson's /Spearman's correlation analysis were used to analyze the correlations between the cross-sectional area of the spinal cord (SC) and individual characteristics; the relationships between the morphology, echogenicity, pulsation, decompression statuses, compression types of SC, location of the spinal cord central echo complex (SCCEC) and the disease severity (the preoperative Japanese Orthopedic Association score, preJOA score); the difference of the spinal cord pulsation amplitude(SCPA) and the SCCEC forward movement rate (FMR) between the compressed areas(CAs) and the non-compressed areas (NCAs). RESULTS: A total of 38 patients were successfully enrolled (30 males and 8 females), and the mean age was 57.05 ± 10.29 (27-75) years. The cross-sectional area of the SC was negatively correlated with age (r = - 0.441, p = 0.006). The preJOA score was significantly lower in the heterogeneous group than in the homogeneous group (P < 0.05, p = 0.005). The hyperechoic area (HEA) was negatively while the SCCEC FMR was positively correlated with the preJOA score (r = - 0.334, p = 0.020; r = 0.286, p = 0.041). The SCCEC FMR and SCPA in CAs were significantly greater than those in NCAs (p < 0.05, p = 0.007; P < 0.001, P = 0.000). CONCLUSION: The cross-sectional area of the SC decreases with age in adults. More changes in intramedullary echogenicity and less moving forward of the SCCEC often indicate poor SC status, and the SCCEC FMR and SCPA are more pronounced in CAs.

Mapping Knowledge Landscapes and Emerging Trends in AI for Dementia Biomarkers: Bibliometric and Visualization Analysis.

BACKGROUND: With the rise of artificial intelligence (AI) in the field of dementia biomarker research, exploring its current developmental trends and research focuses has become increasingly important. This study, using literature data mining, analyzes and assesses the key contributions and development scale of AI in dementia biomarker research. OBJECTIVE: The aim of this study was to comprehensively evaluate the current state, hot topics, and future trends of AI in dementia biomarker research globally. METHODS: This study thoroughly analyzed the literature in the application of AI to dementia biomarkers across various dimensions, such as publication volume, authors, institutions, journals, and countries, based on the Web of Science Core Collection. In addition, scales, trends, and potential connections between AI and biomarkers were extracted and deeply analyzed through multiple expert panels. RESULTS: To date, the field includes 1070 publications across 362 journals, involving 74 countries and 1793 major research institutions, with a total of 6455 researchers. Notably, 69.41% (994/1432) of the researchers ceased their studies before 2019. The most prevalent algorithms used are support vector machines, random forests, and neural networks. Current research frequently focuses on biomarkers such as imaging biomarkers, cerebrospinal fluid biomarkers, genetic biomarkers, and blood biomarkers. Recent advances have highlighted significant discoveries in biomarkers related to imaging, genetics, and blood, with growth in studies on digital and ophthalmic biomarkers. CONCLUSIONS: The field is currently in a phase of stable development, receiving widespread attention from numerous countries, institutions, and researchers worldwide. Despite this, stable clusters of collaborative research have yet to be established, and there is a pressing need to enhance interdisciplinary collaboration. Algorithm development has shown prominence, especially the application of support vector machines and neural networks in imaging studies. Looking forward, newly discovered biomarkers are expected to undergo further validation, and new types, such as digital biomarkers, will garner increased research interest and attention.

Contrast-enhanced US to Improve Diagnostic Performance of O-RADS US Risk Stratification System for Malignancy.

Background The Ovarian-Adnexal Reporting and Data System (O-RADS) has limited specificity for malignancy. Contrast-enhanced US can help distinguish malignant from benign lesions, but its added value to O-RADS has not yet been assessed. Purpose To establish a diagnostic model combining O-RADS and contrast-enhanced US and to validate whether O-RADS plus contrast-enhanced US has a better diagnostic performance than O-RADS alone. Materials and Methods This prospective study included participants from May 2018 to March 2021 who underwent contrast-enhanced US before surgery and had lesions categorized as O-RADS 3, 4, or 5 by US, with a histopathologic reference standard. From April 2021 to July 2022, participants with pathologically confirmed ovarian-adnexal lesions were recruited for the validation group. In the pilot group, the initial enhancement time and enhancement intensity in comparison with the uterine myometrium, contrast agent distribution pattern, and dynamic changes in enhancement of lesions were assessed. Contrast-enhanced US features were used to calculate contrast-enhanced US scores for benign (score ≤2) and malignant (score ≥4) lesions. Lesions were then re-rated according to O-RADS category plus contrast-enhanced US scores. Receiver operating characteristic curves were constructed and compared using the DeLong method. The combined system was validated in an independent group. Results The pilot group included 76 women (mean age, 44 years ± 13 [SD]), and the validation group included 46 women (mean age, 42 years ± 14). Differences in initial enhancement time (P < .001), enhancement intensity (P < .001), and dynamic changes in enhancement (P < .001) between benign and malignant lesions were observed in the pilot group. Contrast-enhanced US scores were calculated using these features. The O-RADS risk stratification was upgraded one level for contrast-enhanced US scores of 4 or more and downgraded one level for contrast-enhanced US scores of 2 or less. In the validation group, the diagnostic performance of O-RADS plus contrast-enhanced US score was higher (area under the receiver operating characteristic curve [AUC] = 0.93) than O-RADS (AUC = 0.71, P < .001). Conclusion Contrast-enhanced US improved the diagnostic performance for malignancy of the O-RADS categories 3-5. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Grant in this issue.

Surveillance for malignant progression of LI-RADS version 2017 category 3/4 nodules using contrast-enhanced ultrasound.

OBJECTIVES: To identify the risk factors for predicting the malignant progression of LR-3/4 observations on the baseline and contrast-enhanced ultrasound (CEUS). METHODS: In total, 245 liver nodules assigned to LR-3/4 in 192 patients from January 2010 to December 2016 were followed up by baseline US and CEUS. The differences in the rate and time of progression to hepatocellular carcinoma (HCC) among subcategories (defined as P1-P7) of LR-3/4 in CEUS Liver Imaging Reporting and Data System (LI-RADS) were analyzed. The risk factors to predict progression to HCC were analyzed by univariate and multivariate Cox proportional hazard model analysis. RESULTS: A total of 40.3% of LR-3 nodules and 78.9% of LR-4 nodules eventually progressed to HCC. The cumulative incidence of progression was significantly higher for LR-4 than LR-3 (p < 0.001). The rate of progression was 81.2% in nodules with arterial phase hyperenhancement (APHE), 64.7% in nodules with late and mild washout, and 100% in nodules with both characteristics. The overall progression rate and median progression time of subcategory P1 nodules (LR-3a) were lower (38.0% vs. 47.6-100.0%) and later (25.1 months vs. 2.0-16.3 months) than those of other subcategories. The cumulative incidence of progression of LR-3a (P1), LR-3b (P2/3/4), and LR-4 (P5/6/7) categories were 38.0%, 52.9%, and 78.9%. The risk factors of HCC progression were Visualization score B/C, CEUS characteristics (APHE, washout), LR-4 classification, echo changes, and definite growth. CONCLUSION: CEUS is a useful surveillance tool for nodules at risk of HCC. CEUS characteristics, LI-RADS classification, and changes in nodules provide useful information for the progress of LR-3/4 nodules. CLINICAL RELEVANCE STATEMENT: CEUS characteristics, LI-RADS classification, and nodule changes provide important predictions for LR-3/4 nodule progression to HCC, which may stratify the risk of malignant progression to provide a more optimized and refined, more cost-effective, and time-efficient management strategy for patients. KEY POINTS: • CEUS is a useful surveillance tool for nodules at risk of HCC, CEUS LI-RADS successfully stratified the risks that progress to HCC. • CEUS characteristics, LI-RADS classification, and changes in nodules can provide important information on the progression of LR-3/4 nodules, which may be helpful for a more optimized and refined management strategy.

US LI-RADS in surveillance for recurrent hepatocellular carcinoma after curative treatment.

OBJECTIVES: To investigate the performance of US LI-RADS in surveillance for recurrent hepatocellular carcinoma (RHCC) after curative treatment. MATERIALS AND METHODS: This study enrolled 644 patients between January 2018 and August 2018 as a derivation cohort, and 397 patients from September 2018 to December 2018 as a validation cohort. The US surveillance after HCC curative treatment was performed. The US LI-RADS observation categories and visualization scores were analyzed. Four criteria using US LI-RADS or Alpha-fetoprotein (AFP) as the surveillance algorithm were evaluated. The sensitivity, specificity, and negative predictive value (NPV) were calculated. RESULTS: A total of 212 (32.9%) patients in derivation cohort and 158 (39.8%) patients in validation cohort were detected to have RHCCs. The criterion of US-2/3 or AFP ≥ 20 µg/L had higher sensitivity (derivation, 96.7% vs 92.9% vs 81.1% vs 90.6%; validation, 96.2% vs 90.5% vs 80.4% vs 89.9%) and NPV (derivation, 95.7% vs 93.3% vs 88.0% vs 91.8%; validation, 94.6% vs 89.4% vs 83.6% vs 89.0%), but lower specificity (derivation, 35.9% vs 48.2% vs 67.6% vs 51.9%; validation, 43.5% vs 52.7% vs 66.1% vs 54.0%) than criterion of US-2/3, US-3, and US-3 or AFP ≥ 20 µg/L. Analysis of the visualization score subgroups confirmed that the sensitivity (89.2-97.6% vs 81.0-83.3%) and NPV(88.4-98.0% vs 80.0-83.3%) of score A and score B groups were higher than score C group in criterion of US-2/3 in both two cohorts. CONCLUSIONS: In the surveillance for RHCC, US LI-RADS with AFP had a high sensitivity and NPV when US-2/3 or AFP ≥ 20 µg/L was considered a criterion. CLINICAL RELEVANCE STATEMENT: The criterion of US-2/3 or AFP ≥ 20 µg/L improves sensitivity and NPV for RHCC surveillance, which provides a valuable reference for patients in RHCC surveillance after curative treatment. KEY POINTS: • US LI-RADS with AFP had high sensitivity and NPV in surveillance for RHCC when considering US-2/3 or AFP ≥ 20 µg/L as a criterion. • After US with AFP surveillance, patients with US-2/3 or AFP ≥ 20 µg/L should perform enhanced imaging for confirmative diagnosis. Patients with US-1 or AFP < 20 µg/L continue to repeat US with AFP surveillance. • Patients with risk factors for poor visualization scores limited the sensitivity of US surveillance in RHCC.

[Analysis of minimally invasive treatment in the management of prostatic abscess].

OBJECTIVE: To analyze the proper time and method for treatment of prostatic abscess (PA). METHODS: This is a retrospective study that included 18 patients diagnosed with and treated for prostatic abscess between February 2017 and July 2022. After obtaining data from the patients' medical records, we analyzed their clinical features as well as the therapeutic methods opted for and their effectiveness. Results： Of the 18 patients included, one achieved a full recovery after a spontaneous rupture of the abscess. Transrectal ultrasound (TRUS)-guided aspiration was performed in the remaining 17 patients, of whom 14 had a complete resolution after this procedure whereas 3 experienced recurrence. The recurrent cases were successfully managed with transurethral (TU) de-roofing. CONCLUSION: TRUS-guided aspiration is a treatment modality with a marked curative effect for simple PAs. For refractory abscesses (recurrent, multifocal, incomplete or unsuccessful drainage) or PA located near the urethra, TU de-roofing can be considered as a first choice to shorten the course of the disease and alleviate the medical treatment expenses due to recurrence.

Association of mitochondrial respiratory chain enzymes with the risk and mortality of sepsis among Chinese children.

BACKGROUND: Sepsis is a leading cause of pediatric morbidity and mortality worldwide. The aim of this study was to explore the association of decreased mitochondrial respiratory chain enzyme activities with the risk for pediatric sepsis, and explore their association with mortality among affected children. METHODS: A total of 50 incident cases with sepsis and 49 healthy controls participated in this study. The level of serum coenzyme Q10 was measured by high-performance liquid chromatography, and selected mitochondrial respiratory chain enzymes in WBC were measured using spectrophotometric. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI). RESULTS: The levels of CoQ10, complex II, complex I + III and FoF1-ATPase were significantly higher in healthy controls than in children with sepsis (p < 0.001, = 0.004, < 0.001 and < 0.001, respectively). In children with sepsis, levels of CoQ10 and complex I + III were significantly higher in survived cases than in deceased cases (p < 0.001). Per 0.05 µmol/L, 50 nmol/min.mg and 100 nmol/min.mg increment in CoQ10, complex I + III and FoF1-ATPase were associated with significantly lowered risk of having sepsis, even after adjusting for confounding factors (OR = 0.85, 0.68 and 0.04, p = 0.001, < 0.001 and < 0.001, respectively). Per 0.05 µmol/L and 50 nmol/min.mg increment in CoQ10 and complex I + III was associated with significantly lowered risk of dying from sepsis during hospitalization, and significance retained after adjustment (OR = 0.73 and 0.76, 95% CI: 0.59 to 0.90 and 0.64 to 0.89, p = 0.004 and 0.001, respectively) in children with sepsis. CONCLUSIONS: Our findings indicate the promising predictive contribution of low serum CoQ10 and complex I + III to the risk of pediatric sepsis and its associated mortality during hospitalization among Chinese children. Trial registration The trial was registered with www.chictr.org.cn , number ChiCTR-IOR-15006446 on May 05, 2015. Retrospectively registered.

AGAMOUS-LIKE67 Cooperates with the Histone Mark Reader EBS to Modulate Seed Germination under High Temperature.

Seed germination is a vital developmental process that is tightly controlled by environmental signals, ensuring germination under favorable conditions. High temperature (HT) suppresses seed germination. This process, known as thermoinhibition, is achieved by activating abscisic acid and inhibiting gibberellic acid biosynthesis. The zinc-finger protein SOMNUS (SOM) participates in thermoinhibition of seed germination by altering gibberellic acid/abscisic acid metabolism, but the underlying regulatory mechanism is poorly understood. In this study, we report that SOM binds to its own promoter and activates its own expression in Arabidopsis (Arabidopsis thaliana) and identify the MADS-box transcription factor AGAMOUS-LIKE67 (AGL67) as a critical player in SOM function, based on its ability to recognize CArG-boxes within the SOM promoter and mediate the trans-activation of SOM under HTs. In addition, AGL67 recruits the histone mark reader EARLY BOLTING IN SHORT DAY (EBS), which recognizes H3K4me3 at SOM chromatin. In response to HTs, AGL67 and EBS are highly enriched around the SOM promoter. The AGL67-EBS complex is also necessary for histone H4K5 acetylation, which activates SOM expression, ultimately inhibiting seed germination. Taken together, our results reveal an essential mechanism in which AGL67 cooperates with the histone mark reader EBS, which bridges the process of H3K4me3 recognition with H4K5 acetylation, thereby epigenetically activating SOM expression to suppress seed germination under HT stress.

Association of mineral metabolism biomarkers with chronic kidney disease in Chinese adults.

BACKGROUND: We aimed to examine the association of three mineral metabolism markers, including serum calcium, inorganic phosphorus, and intact parathyroid hormone with the risk of chronic kidney disease (CKD) at all stages. METHODS: This retrospective cohort study involved 3563 participants, including 3274 CKD patients and 289 healthy controls. CKD is diagnosed according to clinical guidelines from the 2012 KDIGO. Effect sizes are expressed odds ratio (OR) and 95 confidence interval (CI). RESULTS: After propensity score matching, per 0.5 mg/dL increment of inorganic phosphorus was significantly associated with 1.33-, 1.61-, and 2.85-fold increased risk of CKD at stages 1-2, 4, and 5, respectively. Regarding per 8 pg/mL increment of intact parathyroid hormone, significance was only noted for stage 5. In subsidiary analyses, the risk prediction of mineral metabolism markers under study was more evident in males and hypertensive subjects. A nomogram prediction model was constructed based on age, sex, and three mineral metabolism markers for CKD, with decent accuracy. CONCLUSIONS: Our findings indicate that serum calcium was associated with all-stage CKD risk, whereas the association for inorganic phosphorus and intact parathyroid hormone was significant at advanced stages.

Vitamin D Receptor Is a Sepsis-Susceptibility Gene in Chinese Children.

BACKGROUND We designed an association study among 267 cases of children with sepsis and 283 healthy controls, by genotyping 9 variants in the VDR gene. MATERIAL AND METHODS This was a hospital-based, case-control, genetic association study. In addition to 3 genetic modes of inheritance, haplotype and interaction analyses were employed to examine the prediction of VDR gene for pediatric sepsis. Effect-size estimates are expressed as odds ratio (OR) and 95% confidence interval (CI). RESULTS Two variants in the VDR gene, rs2107301 and rs2189480, were found to play a leading role in susceptibility to sepsis in children. The mutant homozygotes of rs2107301 (CC) and rs2189480 (CC) were associated with a reduced risk of sepsis compared with the corresponding wild homozygotes (OR: 0.44 and 0.43, 95% CI: 0.21-0.92 and 0.23-0.81, p: 0.03 and 0.009, respectively). The mutations of rs2107301-C and rs2189480-C alleles were associated with reduced sepsis risk. Haplotype C-C-C-C-C-T-C-A-G in the VDR gene was significantly associated with a 0.59-fold decreased risk of sepsis (95% CI: 0.12-0.76, p: 0.02). In the haplotype-phenotype analysis, significant association was noted for high-density lipoprotein, even after simulation correction (psim <0.05). CONCLUSIONS Taken together, our findings indicate that the VDR gene may be a sepsis-susceptibility gene in Chinese Han children.

The effects of exogenous organic acids on the growth, photosynthesis and cellular ultrastructure of Salix variegata Franch. Under Cd stress.

We studied the effects of three organic acids (citric acid, tartaric acid and malic acid) on the biomass, photosynthetic pigment content and photosynthetic parameters of Salix variegata under Cd stress and observed the ultrastructure of mesophyll cells in each treatment. Cd stress significantly reduced photosynthesis by reducing the content of pigments and disrupting chloroplast structure, which consequently decreased the biomass. However, respective addition of three organic acids greatly increased the biomass of S. variegata under Cd stress. Among them, the effect of malic acid or tartaric acid on shoot and total biomass accumulation was greater than that of citric acid. The alleviation of biomass probably related with the photosynthetic process. Results revealed that treatment with each organic acid enhanced the net photosynthesis rate under Cd stress. Malic acid promoted plant growth and biomass by increasing the chlorophyll content and mitigating damage to the photosynthetic apparatus resulting from Cd stress. Tartaric acid had little impact on the photosynthetic pigment content, but it was important in mitigating the ultrastructural damage of plants caused by Cd. Addition of citric acid significantly increased the carotenoid as well as the number and volume of chloroplasts in mesophyll cells, while the mitigation of structural damage in the photosynthetic apparatus was weaker than that in tartaric acid or malic acid treatment. It is concluded that application of tartaric acid or malic acid is effective in increasing the growth potential of S. variegata under Cd stress and thus can be a promising approach for the phytoremediation of Cd-contaminated soil.

Adeno-associated virus-mediated over-expression of CREB-regulated transcription coactivator 1 in the hippocampal dentate gyrus ameliorates lipopolysaccharide-induced depression-like behaviour in mice.

Depression is a highly complex global disabling psychiatric disorder. Unfortunately, the currently available antidepressants are not effective in a significant percentage of patients. Therefore, the underlying mechanisms of depression must be explored at the molecular level to discover new candidate molecular targets for depression treatment. Behavioural and molecular depression-like endophenotypes have been observed in cyclic AMP response element-binding protein-regulated transcription coactivator 1 (Crtc1) knockout mice; however, the underlying mechanism for these endophenotypes remains unclear. This work investigated the role of hippocampal CREB-regulated transcription coactivator 1 (CRTC1) in depression using a recombinant adeno-associated virus (AAV) system to alter Crtc1 gene expression and explore its potential mechanism. We found that shRNA-mediated Crtc1 gene knockdown (AAV-shCRTC1) in the dentate gyrus regions of the ventral hippocampus directly resulted in depression-like behaviours and down-regulation of brain-derived neurotrophic factor and neuropeptide VGF levels. A widely used depression model induced by lipopolysaccharide administration (0.5 mg/kg, i.p.) was applied in our study and was validated by increased immobility time in the tail-suspension and forced swim tests and decreased sucrose consumption in the sucrose preference test. Importantly, CRTC1 over-expression mediated by AAV-CRTC1 in the ventral dentate gyrus regions prevented lipopolysaccharide-induced depressive-like behaviours, the down-regulation of brain-derived neurotrophic factor and VGF, and the accumulation of pro-inflammatory cytokines such as interleukin-6, interleukin 1-ß and tumour necrosis factor α in mice. Together, our findings indicate that CRTC1 is a key factor in depression-like behaviour and provide an important reference for finding a novel drug target in the neuroinflammatory and neurotrophic pathways for curing depressive disorders. Cover Image for this issue: doi: 10.1111/jnc.14500.

Hemispheric dominance in reading system alters contribution to face processing lateralization across development.

Face processing dominates the right hemisphere. This lateralization can be affected by co-lateralization within the same system and influence between different systems, such as neural competition from reading acquisition. Yet, how the relationship pattern changes through development remains unknown. This study examined the lateralization of core face processing and word processing in different age groups. By comparing fMRI data from 36 school-aged children and 40 young adults, we investigated whether there are age and regional effects on lateralization, and how relationships between lateralization within and between systems change across development. Our results showed significant right hemispheric lateralization in the core face system and left hemispheric lateralization in reading-related areas for both age groups when viewing faces and texts passively. While all participants showed stronger lateralization in brain regions of higher functional hierarchy when viewing faces, only adults exhibited this lateralization when viewing texts. In both age cohorts, there was intra-system co-lateralization for face processing, whereas an inter-system relationship was only found in adults. Specifically, functional lateralization of Broca's area during reading negatively predicted functional asymmetry in the FFA during face perception. This study initially provides neuroimaging evidence for the reading-induced neural competition theory from a maturational perspective in Chinese cohorts.

Association between serum Klotho and major depression: Results from the NHANES 2007-2016 and Mendelian randomization studies.

BACKGROUND: Major depression is a public health problem facing the world. This study aimed to identify the risk factors for major depression and clarify their causal effects. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES). Multifactorial logistic regression analysis was used to calculate the effect of each variable on major depression. Subgroup analyses and interaction tests were conducted to observe the stability of the association between them. Nonlinear correlations were explored using restricted cubic spline plots. The causal effects of serum Klotho on major depression were assessed using Mendelian randomization (MR) analysis. RESULTS: A total of 8359 participated in the study. After adjusting for all covariates, the risk of having major depression was 1.47 times higher for each unit rise in serum Klotho (OR = 1.47, 95 % CI = 1.07-2.02; P = 0.0183). MR analysis showed no causal relationship between serum Klotho levels and risk of major depression (OR = 1.09, 95 % CI = 0.91-1.30; P = 0.4120). Sensitivity analysis verified the reliability of the results. CONCLUSIONS: Serum Klotho is positively associated with an increased risk of major depression in the U.S. population, but MR analyses did not show genetic causality between Klotho and major depression in individuals of European ancestry. Based on the results of the current study, no indication maintaining high levels of Klotho may increase the risk of major depression. LIMITATIONS: The main limitation of this study is the inconsistency of the cross-sectional study and the MR population.

Association between serum methylmalonic acid and chronic kidney disease in adults: a cross-sectional study from NHANES 2013-2014.

Introduction: Chronic kidney disease(CKD) is a global medical problem. Serum methylmalonic acid(MMA) is a serum marker associated with many diseases. This study aimed to investigate the association between MMA and CKD. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were downloaded and analyzed. The association between MMA and CKD was confirmed by using multiple logistic regression modeling. The smooth curve fitting method was used to investigate the nonlinear relationship between them. Subgroup analyses and interaction tests were used to verify the stability of the association between different subgroups. Threshold effect analysis was used to determine the optimal control point for MMA. Results: There was a unique W-shaped nonlinear relationship between MMA and the risk of CKD, with a positive correlation between them (OR=1.66,95% CI:1.27, 2.17; P=0.0002). As the stage of CKD progressed, MMA levels increased. Age, hypertension, and serum vitamin B12 had significant influences on the association between MMA and the risk of CKD. Conclusion: Our findings revealed that serum MMA accumulation was positively associated with the risk of CKD. Serum MMA level may be a novel index to predict the development and course of CKD. This study may help in the early identification of people at risk for chronic kidney disease and provide new ideas and approaches for prevention and treatment.

A comprehensive database of exosome molecular biomarkers and disease-gene associations.

Exosomes play a crucial role in intercellular communication and can be used as biomarkers for diagnostic and therapeutic clinical applications. However, systematic studies in cancer-associated exosomal nucleic acids remain a big challenge. Here, we developed ExMdb, a comprehensive database of exosomal nucleic acid biomarkers and disease-gene associations curated from published literature and high-throughput datasets. We performed a comprehensive curation of exosome properties including 4,586 experimentally supported gene-disease associations, 13,768 diagnostic and therapeutic biomarkers, and 312,049 nucleic acid subcellular locations. To characterize expression variation of exosomal molecules and identify causal factors of complex diseases, we have also collected 164 high-throughput datasets, including bulk and single-cell RNA sequencing (scRNA-seq) data. Based on these datasets, we performed various bioinformatics and statistical analyses to support our conclusions and advance our knowledge of exosome biology. Collectively, our dataset will serve as an essential resource for investigating the regulatory mechanisms of complex diseases and improving the development of diagnostic and therapeutic biomarkers.

Revised Thyroid Imaging Reporting and Data System (TIRADS): imitating the American College of Radiology TIRADS, a single-center retrospective study.

Background: The incidence of thyroid lumps is more and more high in population, and most biopsies of thyroid nodules are benign. To develop a practical risk stratification system based on five ultrasound features to stratify the malignancy risk of thyroid neoplasms. Methods: This retrospective investigation enrolled 999 consecutive patients with 1,236 thyroid nodules who underwent ultrasound screening. Fine-needle aspiration and/or surgery was performed, and pathology results were obtained at the Seventh Affiliated Hospital of Sun Yat-sen University in Shenzhen, China, which is a tertiary referral center, from May 2018 to February 2022. Each thyroid nodule's score was calculated based on five ultrasound features: composition, echogenicity, shape, margin, and echogenic foci. Additionally, each nodule's malignancy rate was calculated. The chi-square test was used to test whether the malignancy rate was different among the three subcategories (scores of 4-6, 7-8, and 9 or more) of thyroid nodules. We proposed the revised Thyroid Imaging Reporting and Data System (R-TIRADS), and its sensitivity and specificity were compared to the two existing systems [the American College of Radiology TIRADS (ACR TIRADS) and the Korean Society of Thyroid Radiology TIRADS (K-TIRADS)]. Results: The final dataset consisted of 425 nodules from 370 patients. The malignancy rates of three subcategories [malignancy rate: 28.8% (scores from 4-6), 64.7% (scores from 7-8), and 84.2% (scores of 9 or more)] were significantly different (P<0.01). The unnecessary biopsy rates of the three systems (ACR TIRADS, R-TIRADS, and K-TIRADS) were 28.7%, 25.2%, and 14.8%, respectively. The R-TIRADS presented better diagnostic performance than the ACR TIRADS or K-TIRADS [area under the curve: 0.79 (95% CI: 0.74-0.83) vs. 0.69 (95% CI: 0.64-0.75), P=0.046; 0.79 (95% CI: 0.74-0.83) vs. 0.66 (95% CI: 0.60-0.71), P=0.041, respectively]. The R-TIRADS had the highest sensitivity [0.746 (95% CI: 0.689-0.803)], followed by the K-TIRADS [0.399 (95% CI: 0.335-0.463), P=0.000] and ACR TIRADS [0.377 (95% CI: 0.314-0.441), P=0.000]. Conclusions: The R-TIRADS enables radiologists to diagnose thyroid nodules efficiently, and the number of unnecessary fine-needle aspirations can be considerably reduced.

Digging out the biology properties of tRNA-derived small RNA from black hole.

An unique subclass of functional non-coding RNAs generated by transfer RNA (tRNA) under stress circumstances is known as tRNA-derived small RNA (tsRNA). tsRNAs can be divided into tRNA halves and tRNA-derived fragments (tRFs) based on the different cleavage sites. Like microRNAs, tsRNAs can attach to Argonaute (AGO) proteins to target downstream mRNA in a base pairing manner, which plays a role in rRNA processing, gene silencing, protein expression and viral infection. Notably, tsRNAs can also directly bind to protein and exhibit functions in transcription, protein modification, gene expression, protein stabilization, and signaling pathways. tsRNAs can control the expression of tumor suppressor genes and participate in the initiation of cancer. It can also mediate the progression of diseases by regulating cell viability, migration ability, inflammatory factor content and autophagy ability. Precision medicine targeting tsRNAs and drug therapy of plant-derived tsRNAs are expected to be used in clinical practice. In addition, liquid biopsy technology based on tsRNAs indicates a new direction for the non-invasive diagnosis of diseases.