An EEG-based marker of functional connectivity: detection of major depressive disorder.

Major depressive disorder (MDD) is a prevalent psychiatric disorder globally. There are many assays for MDD, but rapid and reliable detection remains a pressing challenge. In this study, we present a fusion feature called P-MSWC, as a novel marker to construct brain functional connectivity matrices and utilize the convolutional neural network (CNN) to identify MDD based on electroencephalogram (EEG) signal. Firstly, we combine synchrosqueezed wavelet transform and coherence theory to get synchrosqueezed wavelet coherence. Then, we obtain the fusion feature by incorporating synchrosqueezed wavelet coherence value and phase-locking value, which outperforms conventional functional connectivity markers by comprehensively capturing the original EEG signal's information and demonstrating notable noise-resistance capabilities. Finally, we propose a lightweight CNN model that effectively utilizes the high-dimensional connectivity matrix of the brain, constructed using our novel marker, to enable more accurate and efficient detection of MDD. The proposed method achieves 99.92% accuracy on a single dataset and 97.86% accuracy on a combined dataset. Moreover, comparison experiments have shown that the performance of the proposed method is superior to traditional machine learning methods. Furthermore, visualization experiments reveal differences in the distribution of brain connectivity between MDD patients and healthy subjects, including decreased connectivity in the T7, O1, F8, and C3 channels of the gamma band. The results of the experiments indicate that the fusion feature can be utilized as a new marker for constructing functional brain connectivity, and the combination of deep learning and functional connectivity matrices can provide more help for the detection of MDD.

Determining the Minimal Clinically Important Difference (MCID) and Responsiveness of the Chinese Version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn): A Prospective Multicenter Study.

OBJECTIVES: This study aimed to establish the minimal clinically important difference (MCID) and assess the responsiveness of the Chinese version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn). STUDY DESIGN: Prospective multicenter study. SETTING: Four Chinese tertiary referral centers admitting patients nationwide. PATIENTS: 230 adult patients with chronic otitis media (COM) undergoing tympanoplasty. INTERVENTION: Patients were required to complete the ZCMEI-21-Chn to measure health-related quality of life both preoperatively and postoperatively. An anchor-based method was used to determine the MCID of the derivative cohort by including the Global Rating of Change Questionnaire as an anchor. The generalizability and consistency with functional outcomes of the MCID estimates were externally examined in a validation cohort using a receiver operating characteristic curve analysis. RESULTS: A total of 161 and 69 patients were included in the derivative and validation cohort. The mean preoperative and postoperative ZCMEI-21-Chn total scores were 28.4 (standard deviation [SD] 14.5) and 17.5 (SD 12.6). The mean change in ZCMEI-21-Chn score was 10.9 (SD 14.3, p < 0.001). The MCIDs of the ZCMEI-21-Chn for improvement and deterioration were estimated at 13 (SD 13.0) and -7 (SD 12.9), accordingly. For patients who have reported an improved health-related quality of life, a cutoff value of 15.6 dB HL for elevation of the air-conducted hearing threshold was noticed. However, change of clinical importance judged according to MCID and Japan Otological Society criteria disagreed with each other, notably with a Cohen's kappa ( κ ) of 0.14 ( p = 0.21) in the validation cohort. CONCLUSION: This study is the first to establish the MCID of a COM-specific questionnaire in Chinese. For the COM population undergoing surgical intervention, MCID values of 13 for improvement and -7 for deterioration are recommended. The results were externally validated to be generalizable to nationwide usage, yet distinguishable from the audiological criteria. The availability of the MCID greatly adds to the clinical utility of the ZCMEI-21-Chn by enabling a clinically meaningful interpretation of its score changes.

Cell-free DNA: a promising biomarker in infectious diseases.

Infectious diseases pose serious threats to public health worldwide. Conventional diagnostic methods for infectious diseases often exhibit low sensitivity, invasiveness, and long turnaround times. User-friendly point-of-care tests are urgently needed for early diagnosis, treatment monitoring, and prognostic prediction of infectious diseases. Cell-free DNA (cfDNA), a promising non-invasive biomarker widely used in oncology and pregnancy, has shown great potential in clinical applications for diagnosing infectious diseases. Here, we discuss the most recent cfDNA research on infectious diseases from both the pathogen and host perspectives. We also discuss the technical challenges in this field and propose solutions to overcome them. Additionally, we provide an outlook on the potential of cfDNA as a diagnostic, treatment, and prognostic marker for infectious diseases.

Association of night-time sleep and daytime napping with painful temporomandibular disorder.

BACKGROUND: Painful temporomandibular disorder (TMD) is the common cause of chronic oro-facial pain, which may interfere with sleep. Previous studies have documented an association between sleep and TMD. OBJECTIVES: This study aimed to further explore the association of night-time sleep and daytime napping with painful TMD. METHODS: A total of 419 patients (aged 31.88 ± 11.54 years with women forming 85.4%) from a TMD/Orofacial Pain center were enrolled. Patients' sleep conditions were evaluated with the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and information on night-time sleep duration, napping duration and napping frequency was interviewed. TMD was diagnosed according to the Diagnostic Criteria for TMD protocol and stratified into myalgia (muscle pain), arthralgia (joint pain) and combined (muscle and joint pain) subgroups. The severity of TMD was measured with the Fonseca Anamnestic Index (FAI) questionnaire. Restricted cubic spline (RCS) regression models were established to explore relationships between sleep and painful TMD subgroups. RESULTS: Patients with poor sleep quality (PSQI≥6) had higher FAI scores (median 60, p < .001) and higher proportions of painful TMDs. The myalgia subgroup had higher PSQI scores (median 8, p < .001) than the arthralgia subgroup. The RCS models indicated a non-linear relationship between night-time sleep duration and myalgia (p < .001), which was not observed in arthralgia. However, there were no significant findings concerning napping and painful TMD subgroups. CONCLUSION: This study found that the association between sleep and TMD is mainly related to painful TMD conditions, which are associated with night-time sleep duration.

Randomized Double-Blind Study of the Effect of Injectate Temperature on Intrathecal Bupivacaine Dose Requirement in Spinal Anesthesia for Cesarean Delivery.

BACKGROUND: Increasing the temperature of intrathecal local anesthetics has been shown to increase the speed of onset and block height of spinal anesthesia. However, how this influences dose requirement has not been fully quantified. The aim of this study was to determine and compare the effective dose for anesthesia for cesarean delivery in 50% of patients (ED50) of intrathecal bupivacaine given at temperatures of 37 °C (body temperature) or 24 °C (room temperature). METHODS: Eighty healthy parturients having elective cesarean delivery under combined spinal-epidural anesthesia were randomly assigned to receive intrathecal hyperbaric bupivacaine stored at 37 °C (body temperature group) or 24 °C (room temperature group). The first subject in each group received a bupivacaine dose of 10 mg. The dose for each subsequent subject in each group was varied with an increment or decrement of 1 mg based on the response (effective or noneffective) of the previous subject. Patients for whom the dose was noneffective received epidural supplementation after data collection with lidocaine 2% as required until anesthesia was sufficient for surgery. Values for ED50 were calculated using modified up-down sequential analysis with probit analysis applied as a backup sensitivity analysis. These values were compared and the relative mean potency was calculated. RESULTS: The ED50 (mean [95% confidence interval, CI]) of intrathecal hyperbaric bupivacaine was lower in the body temperature group (6.7 [5.7-7.6] mg) compared with the room temperature group (8.1 [7.7-8.6] mg) (P < .05). The relative potency ratio for intrathecal bupivacaine for the room temperature group versus the body temperature group was 0.84 (95% CI, 0.77-0.93). CONCLUSIONS: Warming hyperbaric bupivacaine to body temperature reduced the dose requirement for spinal anesthesia for cesarean delivery by approximately 16% (95% CI, 7%-23%).

Dimethyl-Dioctadecyl-Ammonium Bromide/Poly(lactic acid) Nanoadjuvant Enhances the Immunity and Cross-Protection of an NM2e-Based Universal Influenza Vaccine.

For most frequent respiratory viruses, there is an urgent need for a universal influenza vaccine to provide cross-protection against intra- and heterosubtypes. We previously developed an Escherichia coli fusion protein expressed extracellular domain of matrix 2 (M2e) and nucleoprotein, named NM2e, and then combined it with an aluminum adjuvant, forming a universal vaccine. Although NM2e has demonstrated a protective effect against the influenza virus in mice to some extent, further improvement is still needed for the induction of immune responses ensuring adequate cross-protection against influenza. Herein, we fabricated a cationic solid lipid nanoadjuvant using poly(lactic acid) (PLA) and dimethyl-dioctadecyl-ammonium bromide (DDAB) and loaded NM2e to generate an NM2e@DDAB/PLA nanovaccine (Nv). In vitro experiments suggested that bone marrow-derived dendritic cells incubated with Nv exhibited ∼4-fold higher antigen (Ag) uptake than NM2e at 16 h along with efficient activation by NM2e@DDAB/PLA Nv. In vivo experiments revealed that Ag of the Nv group stayed in lymph nodes (LNs) for more than 14 days after initial immunization and DCs in LNs were evidently activated and matured. Furthermore, the Nv primed T and B cells for robust humoral and cellular immune responses after immunization. It also induced a ratio of IgG2a/IgG1 higher than that of NM2e to a considerable extent. Moreover, NM2e@DDAB/PLA Nv quickly restored body weight and improved survival of homo- and heterosubtype influenza challenged mice, and the cross-protection efficiency was over 90%. Collectively, our study demonstrated that NM2e@DDAB/PLA Nv could offer notable protection against homo- and heterosubtype influenza virus challenges, offering the potential for the development of a universal influenza vaccine.

Visual psychosocial profiling of Chinese temporomandibular disorder pain patients and correlations with somatosensory function.

BACKGROUND: Psychosocial function of Chinese temporomandibular disorders (TMD) pain patients and the correlation with somatosensory function has not been sufficiently studied. OBJECTIVE: The study aims at assessing the psychosocial function of Chinese TMD pain patients by visualisation method and evaluating the correlations with somatosensory function quantitatively. METHODS: The Symptom Checklist 90 (SCL-90) questionnaire and standardised quantitative sensory testing (QST) were administered to 70 Chinese TMD pain patients and age- and gender-matched healthy controls (HCs). Of these, 40 TMD arthralgia patients received QST before and after medication. Psychosocial and somatosensory parameters were transformed into standardised scores. Differences within groups were assessed through t tests. Correlations between psychosocial and somatosensory profiles were explored through correlation analyses with Bonferroni correction for multiple comparisons. RESULTS: 100% of the Chinese TMD pain patients exhibited psychosocial distress in contrast to HCs. Anger and hostility showed negative correlation with the thermal nonnociceptive parameter (thermal sensory limen, p =.002) and nociceptive parameters (cold pain threshold and pain pressure threshold, p<.001). Correlation analysis indicated that cold detection threshold was negatively correlated with somatization and mechanical pain sensitivity had a negative correlation with anger and hostility through medical treatment (p <.001). CONCLUSIONS: Visual psychosocial profiles provided an easy overview of psychosocial function in Chinese TMD pain patients. Anger and hostility was associated with increased thermal nonnociceptive and nociceptive sensitivity to stimuli. Psychosocial distress might be negatively associated with TMD treatment response which indicated a possible need for psychological intervention during treatment.

Plasma Circulating Cell-Free DNA Facilitated the Detection of an Alveolar Echinococcosis Patient Initially Misdiagnosed as Cystic Echinococcosis: A Case Report.

Echinococcosis, especially alveolar echinococcosis (AE), is becoming an emerging/re-emerging disease with a growing number of cases reported globally. The diagnosis of echinococcosis is based mainly on imaging, which may be challenging when the image presentation is atypical. We reported one patient with suspected cystic echinococcosis (CE) by imaging. The cell-free DNA (cfDNA) obtained from sequencing the patient's plasma before the operation showed that this patient probably had AE with 45 reads mapped to the Echinococcus multilocularis reference genome (Read-Pairs Per Million = 0.24). The patients underwent surgery, and the pathological result showed that the patient had AE. The conventional polymerase chain reaction (PCR) of her lesion sample extraction also indicated that the infection was caused by Echinococcus multilocularis. The follow-up ultrasound after three months indicated no recurrence. We demonstrated that the differentiation of CE and AE by imaging may not be that easy, with further elaboration on the differentiation between AE and CE in different aspects. We demonstrated that it is possible to use patients' plasma cfDNA mapped to Echinococcus references before the operation to obtain the objective clue of the lesion to facilitate diagnosis.

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases.

Macrophages play a critical role in innate immunity, with approximately 90% of the total macrophage population in the human body residing in the liver. This population encompasses both resident and infiltrating macrophages. Recent studies highlight the pivotal role of liver macrophages in various aspects such as liver inflammation, regeneration, and immune regulation. A novel pro-inflammatory programmed cell death, pyroptosis, initially identified in macrophages, has garnered substantial attention since its discovery. Studies investigating pyroptosis and inflammation progression have particularly centered around macrophages. In liver diseases, pyroptosis plays an important role in driving the inflammatory response, facilitating the fibrotic process, and promoting tumor progression. Notably, the role of macrophage pyroptosis cannot be understated. This review primarily focuses on the role of macrophage pyroptosis in liver diseases. Additionally, it underscores the therapeutic potential inherent in targeting macrophage pyroptosis.

Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance.

Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal cancer-derived organoid biobank and induced acquired drug resistance by repeated low-level exposures of chemo-agents. Chemosensitivity profiling and transcriptomic analysis studies revealed that chemoresistant cancer-derived organoids exhibited elevated expression of LGR4 and activation of the Wnt signaling pathway. Further, we generated a monoclonal antibody (LGR4-mAb) that potently inhibited LGR4-Wnt signaling and found that treatment with LGR4-mAb notably sensitized drug-induced ferroptosis. Mechanistically, LGR4-dependent Wnt signaling transcriptionally upregulated SLC7A11, a key inhibitor of ferroptosis, to confer acquired drug resistance. Our findings reveal that targeting of Wnt signaling by LGR4-mAb augments ferroptosis when co-administrated with chemotherapeutic agents, demonstrating a potential opportunity to fight refractory and recurrent cancers.

Prevalence of Adeno-Associated Virus-9-Neutralizing Antibody in Chinese Patients with Duchenne Muscular Dystrophy.

The delivery of a mini-dystrophin gene to skeletal muscles using recombinant adeno-associated virus serotype (AAV) holds great potential as a gene therapy for Duchenne muscular dystrophy (DMD). However, the presence of anti-AAV-neutralizing antibodies (NAbs) may impede the effectiveness of gene transduction. This study aimed to evaluate the prevalence of anti-AAV9 NAbs in Chinese patients with DMD, and to characterize the target population for an AAV gene therapy. A total of one hundred male patients with DMD were included in this study, and demographic and clinical data were collected. A blood specimen was obtained from each participant for the purpose of evaluating the existence of anti-AAV9 NAbs through a cell-based functional assay conducted at a central laboratory. A NAb titer exceeding 1:4 was considered positive. The positivity rates of anti-AAV9 NAb were compared among different subgroups. The median age of this DMD cohort was 8 years old, ranging from 3 to 15 years of age. Forty-two percent of patients tested positive for anti-AAV9 NAb. Notably, all samples from patients under 4 years of age tested negative, and the positivity rates of anti-AAV9 NAb differed significantly across the three age subgroups (<4 years old, ≥4 years old and <12 years old, and ≥12 years old, χ2 = 7.221, p = 0.023). Further investigation into the living environment revealed a higher positivity rate of anti-AAV9 NAb in rural patients compared with urban patients (χ2 = 3.923, p = 0.048). Moreover, the prevalence in patients from different cities/provinces varied greatly (χ2 = 16.550, p = 0.003). There was no statistically significant difference in the positivity rate of NAb among subgroups of patients with different motor functions (ambulatory or nonambulatory) and different treatment strategies (taking or not taking glucocorticoid). In Chinese DMD patients, the prevalence of anti-AAV9 NAb was found to reach 42%. Moreover, the antibody-positive rate in children <4 years of age was low and revealed notable regional discrepancies.

Retrospective study of synovial chondromatosis of the temporomandibular joint: clinical and histopathologic analysis and the early-stage imaging features.

OBJECTIVE: Herein, we aimed to study the clinical, radiographical, and histopathologic features of synovial chondromatosis in the temporomandibular joint (SC in TMJ) and provide references for early diagnosis and treatment prognosis. STUDY DESIGN: The medical records and imaging examinations of patients with SC in TMJ, diagnosed using postoperative histopathologic examination, were reviewed and analyzed. Among them, 18 cases who lacked calcified loose bodies on spiral computed tomography or cone beam computed tomography (SCT/CBCT) were selected for further study. Descriptive statistical methods were used to analyze the clinical characteristics of patients. RESULTS: The study included 100 patients with SC in TMJ, who were predominantly female (male to female: 1:3), and were aged from 21 to 77 years (median, 47). Radiopaque calcified lesions on SCT/CBCT were missing in 18 cases, but cartilaginous nodules were observed during surgery. The cases lacking calcification had a relatively shorter disease course, suggesting they were in the early stages of SC. CONCLUSION: In the early stage of SC, although calcified loose bodies cannot be detected on SCT/CBCT, attention should be paid to the widening of the posterior superior joint space and sclerosis or slight erosion of the joint fossa. Magnetic resonance imaging would be helpful to detect the early-stage SC in TMJ.

Molecularly imprinted polymer sheathed mesoporous silica tube as SPME fiber coating for determination of tobacco-specific nitrosamines in water.

Tobacco-specific nitrosamines (TSNAs) are probably carcinogenic disinfection byproducts eliciting health risk concerns. The determination and surveillance of TSNAs in water is still cumbersome due to the lack of advanced sample preparation methods. Herein, we prepared a solid phase microextraction (SPME) fiber coated with the molecularly imprinted polymer (MIP) sheathed mesoporous silica tube (MST) composite material, and developed a highly efficient, selective, and sensitive method for the determination of five TSNAs in water. Benefiting from the TSNAs-specific recognition of MIP and the increased specific surface area derived from MST, the MIP@MST fiber exhibited excellent extraction performance for TSNAs, which was much superior to the commercially available SPME fibers. By coupling to high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), the outstanding analytical merits such as low method detection limits (ranging 0.1-6.7 ng L-1) and good reproducibility (intra-fiber and inter-fiber relative standard deviations ranging 4.1 %-11.6 % and 3.5 %-12.2 %, respectively) were achieved with the consumption of 8 mL water sample and 100 µL methanol solvent in 50 min. The feasibility of the SPME-HPLC-MS/MS method was demonstrated in tap water and chloraminated source water, with relative recoveries for the five TSNAs ranging from 85.2 % to 108.5 %. In result, none of the TSNAs were found in the tap water samples, while 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-Butanol (NNAL) were detected in the chloraminated source water samples. The rapid and convenient SPME-HPLC-MS/MS method developed in this study offers a powerful tool for monitoring TSNAs in water.

Ecological risk assessment of the typical anti-epidemic drugs in the Pearl River Delta by tracing their source and residual characteristics.

Since the outbreak of the COVID-19 pandemic, the anti-epidemic drugs have been used in extraordinary quantities with high intensity, and concerns have grown about their potential ecological risks due to their continued release and persistence in the receiving environments. A systematic investigation, covering the samples from hospital wastewater, effluent from wastewater treatment plants and receiving water bodies in the Pearl River Delta Region (PRDR), was carried out and aimed at tracing the sources and fate of 30 typical anti-epidemic in different water matrixes and evaluating their ecological risk. The results showed that these typical anti-epidemic drugs residues were detected in most of the sampling sites, with the highest concentration measured in hospital wastewater, whose concentrations were as high as ppb level, while the highest concentration of the surface water samples in tributaries was lower than ppb level. Anti-epidemic drugs contained in hospital wastewater and effluent from WWTPs were the main sources of drug residues in the surface water of this region. In the surface water of PRDR, although the detected concentration anti-epidemic drugs were basically in the range of 0-10 ng/L. The risk quotient of several anti-epidemic drugs, including Ciprofloxacin (CFX), Ofloxacin (OFX), Erythromycin (ETM), Clindamycin (CLI), and Sulfamethoxazole (SMX), was calculated to be a high value, which indicated that they might cause non-negligible ecological risk to the aquatic environment.

Thrombosis density ratio can predict the occurrence of pulmonary embolism and post-thrombotic syndrome in lower-extremity deep vein thrombosis patients.

OBJECTIVE: Deep vein thrombosis (DVT) formation of lower extremities can lead to serious complications including pulmonary embolism (PE) and chronic post-thrombotic syndrome (PTS). We aimed to explore the relationship between the ratio of thrombotic density and the occurrence of PE and PTS in patients with DVT of the lower extremities. METHODS: A retrospective analysis was conducted in patients who performed computed tomography venography, dividing into DVT with PE group (54 patients) and DVT-alone group (34 patients), The clinical data were recorded. Univariate and multivariate logistic regression analysis were used to analysis variables associated with PE. The ability of thrombosis density ratio and Wells score to diagnose PE was evaluated by using the receiver operating characteristic curve (ROC) area under the curve (AUC). According to the treatment and follow-up results, subgroup analysis was performed, and the Villata score was used to determine the presence or absence of PTS and its severity. RESULTS: Compare with the DVT-alone group, more patients had dyspnea and chest pain in the DVT with PE group. DVT with PE group had lower the percentage of neutrophils, white blood cell count and platelet count, while had higher blood cell count, D-dimer, wells score, thrombus and thrombus density ratio. Multivariate logistic analysis showed that percentage of neutrophils (OR(95% CIs)=1.15 (1.01,1.31), P = 0.040), platelets (OR(95% CIs)=0.96 (0.93,0.99), P = 0.011), and thrombus density ratio (OR(95% CIs)=5.99 (1.96,18.35), P = 0.002) are independent predictors of PE. The Wells score and thrombosis density ratio were consistent in the diagnostic efficacy of PE. In the subgroup analysis, there was a relevance between the ratio of thrombosis density and the Villalta score. CONCLUSION: Percentage of neutrophils, platelets, and thrombus density ratio are independent predictors of PE. The thrombosis density of DVT patients may be an index to predict the risk of PE and PTS in DVT patients.

Analysis of Drug-Resistant Tuberculosis in Children in Shenyang, China, 2017-2021.

Objective: Drug-resistant tuberculosis (DR-TB) in children seriously threatens TB control. Information on the epidemiology and characteristics of DR-TB in children in China is limited. We studied data in Shenyang Tenth People's Hospital to understand the DR-TB epidemiology in children in Shenyang. Design or Methods: We retrospectively analyzed drug resistance testing data of pediatric TB patients between 2017 and 2021, and included 2976 clinically-diagnosed pediatric TB patients. We described the epidemiology of DR-TB and analyzed the trends of DR-TB incidence. The Kappa value was calculated to assess the agreement between MGIT 960 DST and Xpert MTB/RIF for detecting rifampicin resistance. Multivariate logistic regression was used to identify the risk factors for DR-TB in pediatric patients. Results: Of the 2976 TB patients, 1076 were confirmed by MGIT 960 culture and/or Xpert MTB/RIF. Among the 806 patients identified by MGIT 960 culture, 232 cases (28.78%) were DR-TB. Resistance to the six drugs was in the following order: streptomycin (21.09%), isoniazid (9.35%), rifampin (15.01%), levofloxacin (6.20%), ethambutol (4.22%), and amikacin (3.23%). Alarmingly, 12.90% were MDR-TB (104/806), including 28 (3.47%) pre-XDR-TB. Of the 1076 pediatric TB patients, 295 (27.4%) developed DR-TB to any one drug (including 69 rifampicin-resistant cases identified by Xpert MTB/RIF only). No difference was found in the incidence of pediatric DR-TB between 2017 and 2021. Among 376 patients who were positive for both methods, using the MGIT 960 DST results as the gold standard, Xpert MTB/RIF's sensitivity for detecting rifampicin resistance was 91.38% and its specificity was 94.65%. Conclusion: Between 2017 and 2021, the DR-TB incidence in children remained unchanged in Shenyang. RR-TB, MDR-TB, and even Pre-XDR-TB require attention in children with drug-resistant TB. Xpert MTB/RIF helped to detect more rifampicin-resistant pediatric patients; thus Xpert MTB/RIF should be widely used as an important complementary tool to detect rifampicin-resistant TB in children.

Quantitative assessment of condylar bone resorption using fused CBCT images: differentiating and diagnosing three distinct groups based on volume and thickness decrease.

OBJECTIVES: To investigate the accuracy of fused CBCT images in diagnosing three distinct groups of bone changes characterized by volume and thickness decrease in patients with temporomandibular joint osteoarthrosis (TMJ OA) during follow-up. METHODS: In this retrospective study, 109 patients (176 TMJs) with TMJ OA were included. Two consecutive CBCT images for the same patient were registered and fused. Then, three image sets were established: without fusion, fused 2D image, and fused 3D image. Three residents randomly and independently evaluated whether there was condylar resorption with the three image sets respectively. The samples diagnosed as condylar resorption by the expert panel were divided into three subgroups according to the volume and thickness decrease calculated after segmentation. The inter- and intraobserver agreement, receiver operating characteristic (ROC), and area under the curve (AUC) evaluated the diagnostic capability for different subgroups. RESULTS: For the volume decrease more than 50 mm3 and thickness decrease more than 1 mm groups, the AUC values for fused image sets were higher than those without fusion (p < 0.01). For the volume decrease within 50 mm3 and thickness decrease within 1 mm groups, the AUC values for fused 2D image sets were higher than the image sets without fusion (p < 0.05), but there was no significant difference between the fused 3D image sets and the image sets without fusion (p = 0.48 for volume decrease, p = 0.37 for thickness decrease). CONCLUSIONS: The fused images can improve the diagnostic accuracy and repeatability for the samples with at least 50 mm3 volume decrease or 1 mm thickness decrease compared with the image groups without fusion.

NRF1-mediated mitochondrial biogenesis antagonizes innate antiviral immunity.

Mitochondrial biogenesis is the process of generating new mitochondria to maintain cellular homeostasis. Here, we report that viruses exploit mitochondrial biogenesis to antagonize innate antiviral immunity. We found that nuclear respiratory factor-1 (NRF1), a vital transcriptional factor involved in nuclear-mitochondrial interactions, is essential for RNA (VSV) or DNA (HSV-1) virus-induced mitochondrial biogenesis. NRF1 deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in mice. Mechanistically, the inhibition of NRF1-mediated mitochondrial biogenesis aggravated virus-induced mitochondrial damage, promoted the release of mitochondrial DNA (mtDNA), increased the production of mitochondrial reactive oxygen species (mtROS), and activated the innate immune response. Notably, virus-activated kinase TBK1 phosphorylated NRF1 at Ser318 and thereby triggered the inactivation of the NRF1-TFAM axis during HSV-1 infection. A knock-in (KI) strategy that mimicked TBK1-NRF1 signaling revealed that interrupting the TBK1-NRF1 connection ablated mtDNA release and thereby attenuated the HSV-1-induced innate antiviral response. Our study reveals a previously unidentified antiviral mechanism that utilizes a NRF1-mediated negative feedback loop to modulate mitochondrial biogenesis and antagonize innate immune response.