Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort.

BACKGROUND: Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage. METHODS: SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes. FINDINGS: Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79). CONCLUSION: This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients. FUNDING: This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

Fabrication of versatile Fe3O4/GO/Au composite nanomaterial as SERS-active substrate for detection of pesticide residue.

Highly active Fe3O4/GO/Au composite nanomaterial was fabricated as a substrate of surface-enhanced Raman spectroscopy (SERS) and applied for pesticide residue detection. The three-layer multifunctional Fe3O4/GO/Au nanoparticles (NPs) were designed by facile method, with high hotspots, and were characterized by various techniques, including ultraviolet spectrophotometry (UV), X-ray diffraction (XRD), infrared absorption spectrometer (IR), and transmission electron microscopy (TEM). The performance of Fe3O4/GO/Au was evaluated by Raman spectroscopy with R6G as a probe molecule to verify its enhancement effect. It exhibited a strong Raman signal with 10-6 M of R6G. Furthermore, the presence of Fe3O4/GO/Au nanohybrid enabled the SERS-based method to detect mancozeb and showed an excellent linear relationship in the range of 0.25-25 ppm, with a low limit of detection (0.077 ppm), satisfactory EF, stability, and repeatability. In addition, the mechanism of SERS enhancement with electromagnetic mechanism (EM) and chemical mechanism (CM) was discussed in detail. Therefore, the proposed SERS approach holds promise as an auxiliary technique for screening contaminated agricultural products, environmental sample, and food in the future.

MOF-Derived Zn/N-Doped Porous Carbon Film on a Carbon Nanotube for High-Performance Supercapacitors.

Designing high-performance binder-free electrochemical electrodes is crucially important toward supercapacitors. In this paper, a Zn/N-doped porous carbon film coating on flexible carbon nanotubes (ZIF-8@CT-800) derived from the epitaxial Zn-MOF film growth on cotton textile was successfully fabricated via a combination of the liquid-phase epitaxial (LPE) method and calcination treatments. The ZIF-8@CT-800 serves directly as a self-supported electrode for supercapacitors and exhibits a high areal capacitance of 930 mF·cm-2 at a current density of 1 mA·cm-2 and a good recyclability of 86% after 2000 cycles. The excellent supercapacitor property is ascribed to the unique structural design of ZIF-8@CT-800, which provides appropriate channels for enhanced electronic and ionic transport as well as increased surface area for accessing more electrolyte ions. This work will provide significant guidance for designing MOF-derived porous carbon to construct flexible binder-free electrode materials with high electrochemical performance.

Sparse transformer with local and seasonal adaptation for multivariate time series forecasting.

Transformers have achieved remarkable performance in multivariate time series(MTS) forecasting due to their capability to capture long-term dependencies. However, the canonical attention mechanism has two key limitations: (1) its quadratic time complexity limits the sequence length, and (2) it generates future values from the entire historical sequence. To address this, we propose a Dozer Attention mechanism consisting of three sparse components: (1) Local, each query exclusively attends to keys within a localized window of neighboring time steps. (2) Stride, enables each query to attend to keys at predefined intervals. (3) Vary, allows queries to selectively attend to keys from a subset of the historical sequence. Notably, the size of this subset dynamically expands as forecasting horizons extend. Those three components are designed to capture essential attributes of MTS data, including locality, seasonality, and global temporal dependencies. Additionally, we present the Dozerformer Framework, incorporating the Dozer Attention mechanism for the MTS forecasting task. We evaluated the proposed Dozerformer framework with recent state-of-the-art methods on nine benchmark datasets and confirmed its superior performance. The experimental results indicate that excluding a subset of historical time steps from the time series forecasting process does not compromise accuracy while significantly improving efficiency. Code is available at https://github.com/GRYGY1215/Dozerformer.

Discovery of NO Donor-Aurovertin Hybrids as Dual Ferroptosis and Apoptosis Inducers for Treating Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure-activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.

KOH-activated hollow carbon spheres with surface functionalization for high-capacity and long-cycle-life lithium-selenium batteries.

Lithium-selenium (Li-Se) batteries are considered promising alternatives to lithium-ion batteries due to their higher volumetric capacity and energy density. However, they still face limitations in efficiently utilizing the active selenium. Here, we develop surface-functionalized mesoporous hollow carbon nanospheres as the selenium host. By using KOH activation, the surface of the carbon nanospheres is functionalized with hydroxyl groups, which greatly improve the utilization of selenium and facilitate the conversion of lithium selenides, leading to much higher capacities compared to ZnCl2 activation and untreated carbon nanospheres. Theory and experimental evidence suggest that surface hydroxyl groups can enhance the reduction conversion of polyselenides to selenides and facilitate the oxidation reaction of selenides to elemental selenium. In-situ and ex-situ characterization techniques provided additional confirmation of the hydroxyl groups electrochemical durability in catalyzing selenium conversion. The meticulously engineered Se cathode demonstrates a high specific capacity of 594 mA h g-1 at 0.5C, excellent rate capability of 464 mA h g-1 at 2C, and a stable cycling performance of 500 cycles at 2C with a capacity retention of 84.8 %, corresponding to an ultra-low-capacity decay rate of 0.0144 % per cycle, surpassing many reported lithium-selenium battery technologies.

Retinal thickness and microvascular alterations observed by optical coherence tomography in antineutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional study.

Background: As an autoimmune disease, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) often affects multiple organs, including the ocular system. This study aims to investigate differences in retinal thickness (RT) and retinal superficial vascular density (SVD) between patients with AAV and healthy controls (HCs) using optical coherence tomography angiography (OCTA). Currently, these differences are not clear. Methods: A total of 16 AAV individuals (32 eyes) and 16 HCs (32 eyes) were recruited to this cross-sectional study conducted in the First Affiliated Hospital of Nanchang University from June 2023 to September 2023. The study protocol conformed with the tenets of the Declaration of Helsinki (as revised in 2013). Each image observed by OCTA was divided into 9 regions using the Early Treatment Diabetic Retinopathy Study (ETDRS) subzones as a guide. Results: In the full layer, the RT of AAV patients was found to be significantly reduced in the inner superior (IS, P<0.001), outer superior (OS, P=0.003), inner temporal (IT, P=0.003), and outer temporal (OT, P<0.001) regions; inner RT was significantly lower in the IS (P=0.006), OS (P<0.001), inner nasal (IN, P=0.005), outer nasal (ON, P<0.001), and center (C, P=0.01) regions than that in HCs. Outer RT of AAV patients showed a reduction in the IS (P<0.001), as well as IT (P=0.008), and OT (P<0.001) regions. No statistically significant differences were seen in the different subregions in other different layers (P>0.05). Only the inner inferior (II) and outer inferior (OI) regions of SVD in AAV patients did not differ significantly from controls. All other regions showed a reduction in SVD. The details are as follows: IS (P<0.001), OS (P<0.001), IT (P=0.005), OT (P<0.001), IN (P<0.001), ON (P<0.001), and C (P=0.003). According to receiver operating characteristic (ROC) curve analysis, the full IS region [area under the curve (AUC): 0.8892, 95% confidence interval (CI): 0.8041-0.9742, P<0.001] had the highest diagnostic value for AAV-induced reduction in RT. The IS (AUC: 0.9121, 95% CI: 0.8322-0.9920, P<0.001) region was also the most sensitive to changes in SVD of AAV individuals. In addition, we found that SVD in the IN region (r=-0.4224, 95% CI: -0.6779 to -0.0757, P=0.02) as well as mean visual acuity (r=-0.3922, 95% CI: -0.6579 to -0.0397, P=0.03) of AAV patients were negatively correlated with disease duration. However, we did not find an association between SVD and RT in this study. Conclusions: The findings from OCTA indicated a reduction in RT and SVD among patients with AAV. OCTA allows for the evaluation of AAV-related ocular lesions and holds promise for monitoring of disease progression through regular evaluations.

Lower-extremity deep vein thrombosis induced by oxaliplatin and capecitabine chemotherapy: A case report.

Oxaliplatin and capecitabine are instrumental in the adjunctive and palliative systemic management of colorectal cancer. The concurrent administration of these chemotherapeutic agents often results in adverse effects, such as nausea, vomiting, diarrhea, leukopenia, and hand-foot syndrome. However, reports of deep vein thrombosis (DVT) caused by oxaliplatin and capecitabine are scarce. In this case study, we report a rare occurrence of lower-extremity DVT triggered by synergistic oxaliplatin and capecitabine chemotherapy in a patient diagnosed with malignant colon cancer. During the initial cycle of chemotherapy, the patient demonstrated DVT within the intermuscular veins of the right calf and abnormalities in markers of coagulation function. Enlargement of the intermuscular venous thrombosis and an increase in coagulation markers were observed subsequent to the second chemotherapy cycle. From our experience of this case, we suggest that DVT is induced by oxaliplatin and capecitabine warrants vigilant attention. Risk assessment for DVT prior to chemotherapy, coupled with early detection and intervention, is crucial for DVT prevention. Furthermore, enhancing the awareness of health care professionals and patients about the potential of chemotherapy-induced DVT is of paramount importance. Consequently, this case carries significant clinical implications.

Symptom progression in neuromyelitis optica spectrum disorder from ataxia through syncope to neuropathic pain: A case report.

RATIONALE: Neuromyelitis optica spectrum disorder (NMOSD) involves autoimmune and inflammatory responses in the central nervous system, primarily affecting the optic nerves and spinal cord. Atypical presentations such as ataxia and syncope complicate the diagnosis, and lesions in the medulla are easily mistaken for cerebral infarction. This case report emphasizes the need to recognize such manifestations to avoid misdiagnosis and ensure timely treatment. PATIENT CONCERNS: This case report presents an NMOSD female patient who experienced ataxia, syncope, and neuropathic pain during her illness. DIAGNOSIS: NMOSD. INTERVENTIONS: The patient managed her blood sugar with insulin, controlled neuropathic pain with pregabalin, and underwent 5 plasma exchanges. OUTCOMES: Significant improvement was noted 1 week post-plasma exchange, with complete resolution of neuropathic pain and no symptom recurrence reported at 6-month follow-up. LESSONS: Atypical manifestations of NMOSD, such as ataxia, syncope, and trigeminal neuralgia, increase diagnostic difficulty. Recognizing these symptoms is crucial to avoid misdiagnosis and ensure timely and appropriate treatment for patients.

Axial Ligand Enables Synthesis of Allenylsilane through Dirhodium(II) Catalysis.

Described herein is a dirhodium(II)-catalyzed silylation of propargyl esters with hydrosilanes, using tertiary amines as axial ligands. By adopting this strategy, a range of versatile and useful allenylsilanes can be achieved with good yields. This reaction not only represents a SN2'-type silylation of the propargyl derivatives bearing a terminal alkyne moiety to synthesize allenylsilanes from simple hydrosilanes, but also represents a new application of dirhodium(II) complexes in catalytic transformation of carbon-carbon triple bond. The highly functionalized allenylsilanes that are produced can be transformed into a series of synthetically useful organic molecules. In this reaction, an intriguing ON-OFF effect of the amine ligand was observed. The reaction almost did not occur (OFF) without addition of Lewis base amine ligand. However, the reaction took place smoothly (ON) after addition of only catalytic amount of amine ligand. Detailed mechanistic studies and density functional theory (DFT) calculations indicate that the reactivity can be delicately improved by the use of tertiary amine. The fine-tuning effect of the tertiary amine is crucial in the formation of the Rh-Si species via a concerted metalation deprotonation (CMD) mechanism and facilitating ß-oxygen elimination.

Downregulation of HDAC6 mitigates lung ischemia/reperfusion injury depending on activation of Nrf2/HO-1 signaling pathway and inactivation of ERK/NF-κB signaling pathway.

INTRODUCTION: Lung ischemia/reperfusion injury (LIRI) is a pathological process caused by the deficiency and subsequent reperfusion of oxygen and blood to the lung. Literature reports that the catalytic activity and expression of HDAC6 can be induced in response to IRI. HDAC6 inhibition confers protective effects against a series of IRI and also exerts pulmonary protection against various lung damage. The present study was formulated to investigate the functional role of HDAC6 inhibitor in LIRI and to probe into the intrinsic mechanisms underlying the protective role of HDAC6 inhibitor against LIRI. METHODS: Lung epithelial cell line MLE-12 cells were subjected to H/R injury to construct in vitro cell culture model of LIRI. For functional experiments, MLE-12 cells were pre-treated with various concentrations of selective HDAC6 inhibitor ACY-1215 (1, 5, 10 µM) to evaluate the biological role of HDAC6 in LIRI. For rescue experiments, MLE-12 cells were pre-treated with Nrf2 inhibitor ML385 (10 µM) or ERK activator LM22B-10 (50 µM) to discuss the molecular mechanisms. RESULTS: It was verified that HDAC6 inhibition repressed H/R-induced apoptosis, oxidative stress, inflammation and mitochondrial dysfunction of MLE-12 cells. HDAC6 inhibition activated Nrf2/HO-1 signaling pathway and inactivated ERK/NF-κB signaling pathway in MLE-12 cells. The repressing effects of HDAC6 inhibition on H/R-induced apoptosis, oxidative stress, inflammation and mitochondrial dysfunction of MLE-12 cells were partially abolished upon pre-treatment with Nrf2 inhibitor ML385 or ERK activator LM22B-10. CONCLUSION: HDAC6 inhibition may mitigate H/R-induced lung epithelial cell injury depending on activation of Nrf2/HO-1 signaling pathway and inactivation of ERK/NF-κB signaling pathway.

CRASH2p: Closed-loop Two Photon Imaging in Freely Moving Animals.

Direct measurement of neural activity in freely moving animals is essential for understanding how the brain controls and represents behaviors. Genetically encoded calcium indicators report neural activity as changes in fluorescence intensity, but brain motion confounds quantitative measurement of fluorescence. Translation, rotation, and deformation of the brain and the movements of intervening scattering or auto-fluorescent tissue all alter the amount of fluorescent light captured by a microscope. Compared to single-photon approaches, two photon microscopy is less sensitive to scattering and off-target fluorescence, but more sensitive to motion, and two photon imaging has always required anchoring the microscope to the brain. We developed a closed-loop resonant axial-scanning high-speed two photon (CRASH2p) microscope for real-time 3D motion correction in unrestrained animals, without implantation of reference markers. We complemented CRASH2p with a novel scanning strategy and a multistage registration pipeline. We performed volumetric ratiometrically corrected functional imaging in the CNS of freely moving Drosophila larvae and discovered previously unknown neural correlates of behavior.

[Retracted] Effect of metformin on cell proliferation, apoptosis, migration and invasion in A172 glioma cells and its mechanisms.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell invasion and migration assay data shown in Fig. 6 and the cell proliferation assay experiments shown in Fig. 2 were strikingly similar to data appearing in different form in other articles by different authors; furthermore, in Fig. 2, for the '10 mM metformin' experiment, certain of the glioma cells appeared to be strikingly similar to other cells contained within the same data panels. Owing to the fact that the contentious data in the above article had already been published elsewhere or were under consideration for publication prior to its submission to Molecular Medicine Reports, and owing to concerns with the authenticity of certain of the data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 887­894, 2019; DOI: 10.3892/mmr.2019.10369].

The BLV-miRNAs pathway of BLV inhibits the expression of Lactoferrin, Lactoperoxidase, Alpha-lactalbumin and Beta-lactoglobulin proteins.

Bovine leukemia virus (BLV) is a widespread virus that decreases milk production and quality in dairy cows. As crucial components of BLV, BLV-encoded microRNAs (BLV-miRNAs) affect BLV replication and may impact the synthesis of Lactoferrin (LTF), Lactoperoxidase (LPO), Alpha-lactalbumin (alpha-LA), and Beta-lactoglobulin (beta-LG). In this study, we investigated the targeting relationship between BLV-miRNAs and LTF, LPO, alpha-LA, and beta-LG in cow's milk. Additionally, we investigated the possible mechanisms by which BLV reduces milk quality. The results showed that cow's milk had significantly lower levels of LTF, LPO, and alpha-LA proteins in BLV-positive cows than in BLV-negative cows. BLV-△miRNAs (miRNA-deleted BLV) enhanced the reduction of LPO, alpha-LA, and beta-LG protein levels caused by BLV infection. Multiple BLV-miRNAs have binding sites with LTF and LPO mRNA; however, only BLV-miR-B1-5 P has a targeting relationship with LPO mRNA. The results revealed that BLV-miR-B1-5 P inhibits LPO protein expression by targeting LPO mRNA. However, BLV does not directly regulate the expression of LTF, alpha-LA, or beta-LG proteins through BLV-miRNAs.

Whole-exome sequencing in a cohort of Chinese patients with isolated cervical dystonia.

Background: Dystonia is a kind of movement disorder but its pathophysiological mechanisms are still largely unknown. Recent evidence reveals that genetical defects may play important roles in the pathogenesis of dystonia. Objectives and Methods: -To explore possible causative genes in Chinese dystonia patients, DNA samples from 42 sporadic patients with isolated cervical dystonia were subjected to whole-exome sequencing. Rare deleterious variants associated with dystonia phenotype were screened out and then classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Phenolyzer was used for analyzing the most probable candidates correlated with dystonia phenotype, and SWISS-MODEL server was for predicting the 3D structures of variant proteins. Results: Among 42 patients (17 male and 25 female) recruited, a total of 36 potentially deleterious variants of dystonia-associated genes were found in 30 patients (30/42, 71.4 %). Four disease-causing variants including a pathogenic variant in PLA2G6 (c.797G > C) and three likely pathogenic variants in DCTN1 (c.73C > T), SPR (c.1A > C) and TH (c.56C > G) were found in four patients separately. Other 32 variants were classified as uncertain significance in 26 patients. Phenolyzer prioritized genes TH, PLA2G6 and DCTN1 as the most probable candidates correlated with dystonia phenotype. Although 3D prediction of DCTN1 and PLA2G6 variant proteins detected no obvious structural alterations, the mutation in DCTN1 (c.73C > T:p.Arg25Trp) was closely adjacent to its key functional domain. Conclusion: Our whole-exome sequencing results identified a novel variant in DCTN1 in sporadic Chinese patients with isolated cervical dystonia, which however, needs our further study on its exact role in dystonia pathogenesis.

Discovery of Aurovertin B as a Potent Metastasis Inhibitor against Triple-Negative Breast Cancer: Elucidating the Complex Role of the ATF3-DUSP1 Axis.

Triple-negative breast cancer (TNBC) is characterized by high mortality rates primarily due to its propensity for metastasis. Addressing this challenge necessitates the development of effective antimetastatic therapies. This study aimed to identify natural compounds with potential antimetastatic properties mainly based on the high-throughput phenotypic screening system. This system, utilizing luciferase reporter gene assays combined with scratch wound assays, evaluates compounds based on their influence on the epithelial-mesenchymal transition (EMT) marker E-cadherin. Through this approach, aurovertin B (AVB) was revealed to have significant antimetastatic capability. Notably, AVB exhibited substantial metastasis suppression in many TNBC cell lines, including MDA-MB-231, HCC1937 and 4T1. Also, its remarkable antimetastatic activity was demonstrated in vivo via the orthotopic breast cancer mouse model. Further exploration revealed a pronounced association between AVB-induced upregulation of DUSP1 (dual-specificity phosphatase 1) and its inhibitory effect on TNBC metastasis. Additionally, microarray analysis conducted to elucidate the underlying mechanism of the AVB-DUSP1 interaction identified ATF3 (activating transcription factor 3) as a critical transcription factor instrumental in DUSP1 transcriptional activation. This discovery, coupled with observations of enhanced ATF3-DUSP1 expression and consequent reduction in TNBC metastatic foci in response to AVB, provides novel insights into the molecular mechanisms driving metastasis in TNBC. Significance Statement We construct a high-throughput phenotypic screening system utilizing EMT marker E-cadherin promoter luciferase reporter gene combined with scratch wound assays. Aurovertin B was revealed to possess significant antimetastatic activity through this approach, which was further demonstrated via in vivo and in vitro experiments. The discovery of the regulatory role of the ATF3-DUSP1 pathway enriches our understanding of TNBC metastasis mechanism and suggests the potential of ATF3 and DUSP1 as biomarkers for diagnosing TNBC metastasis.

Transformer-based Multi-label Deep Learning Model is Efficient for Detecting Ankle Lateral and Medial Ligament Injuries on MRI and Improving Clinicians' Diagnostic Accuracy for Rotational Chronic Ankle Instability.

PURPOSE: To develop a deep learning (DL) model that can simultaneously detect lateral and medial collateral ligament injuries of the ankle, aiding in the diagnosis of chronic ankle instability (CAI), and assess its impact on clinicians' diagnostic performance. METHODS: DL models were developed and external validated on retrospectively collected ankle MRIs between April 2016 and March 2022 respectively at three centers. Included patients were confirmed diagnoses of CAI through arthroscopy, as well as individuals who had undergone MRI and physical examinations that ruled out ligament injuries. DL models were constructed based on a multi-label paradigm. A transformer-based multi-label DL model (AnkleNet) was developed and compared with four convolution neural network (CNN) models. Subsequently, a reader study was conducted to evaluate the impact of model assistance on clinicians when diagnosing challenging cases: identifying rotational CAI (RCAI). Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: Our transformer-based model achieved AUC of 0.910 and 0.892 for detecting lateral and medial collateral ligament injury, respectively, both of which was significantly higher than that of CNN-based models (all P < 0.001). In terms of further CAI diagnosis, it exhibited a macro-average AUC of 0.870 and a balanced accuracy of 0.805. The reader study indicated that incorporation with our model significantly enhanced the diagnostic accuracy of clinicians (P = 0.042), particularly junior clinicians, and led to a reduction in diagnostic variability. The code of the model can be accessed at https://github.com/ChiariRay/AnkleNet. CONCLUSION: Our transformer-based model was able to detect lateral and medial collateral ligament injuries based on MRI and outperformed CNN-based models, demonstrating a promising performance in diagnosing CAI, especially RCAI patients.

Exploring the interplay of weight-based teasing and sociodemographic factors in adolescent weight bias internalization.

OBJECTIVE: Research has highlighted the potential adverse effects of weight bias internalization (WBI) on adolescents, but there has been little examination of WBI and sources of weight teasing (family, peers, or both) or across racial/ethnic diversity of adolescents. We aimed to examine the relationship between WBI and sources of weight teasing across sociodemographic characteristics and weight status in a diverse community sample of adolescents. METHODS: Data were collected from a U.S. sample of 1859 adolescents aged 10-17 years (59% female; 43% White, 27% Black or African American, and 25% Latino). An online questionnaire was used to assess participants' experiences of weight teasing from family members, peers, or both, and their weight status, weight-related goals, WBI, and sociodemographic characteristics. RESULTS: Adolescents experiencing weight teasing from both family and peers reported the highest levels of WBI, while those reporting no teasing exhibited the lowest levels. These patterns were observed across sex, race/ethnicity, weight status, and weight goals, and persisted after controlling for depressive symptoms. Notably, family influences played a salient role, with adolescents reporting higher WBI if teased by family only compared to teasing from peers only. Sex and racial differences were also observed in adolescents' experiences with weight-based teasing. CONCLUSION: Our study reveals associations between adolescent weight-based teasing, WBI, and sociodemographic factors. Weight-based teasing, whether from family and peers or from family only, was associated with increased WBI. Interventions targeting weight stigma in youth should not be limited to peer-focused efforts, but should also emphasize supportive family communication.

A Cysteinyl-tRNA Synthetase Mutation Causes Novel Autosomal-Dominant Inheritance of a Parkinsonism/Spinocerebellar-Ataxia Complex.

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture.

Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice.

Injuries to the brain result in tunable cell responses paired with stimulus properties, suggesting the existence of intrinsic processes that encode and transmit injury information; however, the molecular mechanism of injury information encoding is unclear. Here, using ATP fluorescent indicators, we identify injury-evoked spatiotemporally selective ATP dynamics, Inflares, in adult mice of both sexes. Inflares are actively released from astrocytes and act as the internal representations of injury. Inflares encode injury intensity and position at their population level through frequency changes and are further decoded by microglia, driving changes in their activation state. Mismatches between Inflares and injury severity lead to microglia dysfunction and worsening of injury outcome. Blocking Inflares in ischemic stroke in mice reduces secondary damage and improves recovery of function. Our results suggest that astrocytic ATP dynamics encode injury information and are sensed by microglia.