First-line treatment with KN046, chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma: an open-label, dose escalation, and dose expansion phase Ib trial.

There is growing evidence to suggest that radiotherapy might enhance the efficacy of immunotherapy. This study aimed to assess the possibility of KN046, a bispecific antibody targeting PD-L1 and CTLA-4, combined with chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma (ESCC). In this open-label, phase Ib trial, patients with advanced ESCC were administered chemotherapy with palliative radiotherapy, and KN046 in the predefined escalation dosages of 1, 3, or 5 mg/kg (every 3 weeks during chemotherapy cycles and every 2 weeks during KN046 maintenance). The chemotherapy regimen constituted cisplatin (75 mg/m2 i.v., d1) and paclitaxel (135-175 mg/m2 ivgtt., d1). Radiotherapy specifics, including site, timing, dose, and fragmentation pattern, were at the investigator's discretion. The primary outcome was dose-limiting toxicity (DLT). From May 2019 to April 2021, 25 patients were enrolled across the dosage groups: 3 in 1 mg/kg, 12 in 3 mg/kg, and 10 in 5 mg/kg. No DLT was observed during the dose escalation. The objective response rate was 41.7% (95%CI 22.1-63.4), while the disease control rate was 87.5% (95%CI 67.6-97.3). At a median follow-up of 11.8 months, the median progression-free survival was 7.8 months (95%CI 5.2-9.7) and median overall survival was 15.9 months (95%CI 8.4-NE). Serious adverse events were reported in 48.0% of patients, predominantly leukopenia (16%), immune-mediated enterocolitis (12%), immune-mediated pneumonitis (8%), and neutropenia (8%). Combining KN046 with chemotherapy and palliative radiotherapy might be feasible, showing a favorable safety profile and notable efficacy in advanced ESCC patients.

Role of effective atomic number of paraspinal muscles in the prediction of acute vertebral fracture risk assessment: a cross-sectional case-control study.

OBJECTIVES: We aim to investigate the relations among effective atomic number (Zeff), density, and area of paraspinal muscles, volumetric bone mineral density (vBMD), and acute vertebral fractures (VF) by using spectral base images (SBIs) and routine CT images. METHODS: A total of 223 patients (52 men and 171 women) with acute lumber VF and 776 subjects (286 men and 390 women) without VF of at least 60 years were enrolled and underwent dual-layer detector CT scans. We quantified the cross-sectional area, density (paraSMD), and Zeff of paraspinal muscles by CT images and SBIs and measured vBMD of the lumbar spine by quantitative CT. RESULTS: Higher vBMD was associated with lower VF risk in both sexes (adjusted OR, 0.33 and 0.43). After adjusting for age and body mass index, the associations of paraSMD with VF were not significant in men, and in women the association was borderline significant (OR, 0.80; 95% CI, 0.64-1.00). However, higher Zeff of paraspinal muscles was associated with lower VF risk in men (adjusted OR, 0.59; 0.36-0.96) but not in women. The associations of all muscle indexes with VF were not significant after further adjusting for vBMD. CONCLUSIONS: A higher Zeff of paraspinal muscles is associated with lower VF risk in older men but not in older women. The density, area, and Zeff of paraspinal muscles were not vBMD independent risk factors for acute VF. ADVANCES IN KNOWLEDGE: The effective atomic number of paraspinal muscles might be a potential marker for VF risk prediction.

Treatment of lumbar disc herniation with robot combined with unilateral biportal endoscopic technology: A case report.

BACKGROUND: This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion (UBE-LIF), utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment, and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw placement. The advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies, and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients, and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for reference. CASE SUMMARY: A 44-year-old patient presented to our hospital. Combining various clinical data, we diagnosed the patient with lumbar disc herniation with radiculopathy, lumbar spondylolisthesis, and lumbar spinal stenosis. We developed a surgical plan of "UBE decompression + UBE-LIF + orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation". The results were satisfactory. CONCLUSION: We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good results. Therefore, the technique is worthy of clinical promotion.

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

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

MiR-127-3p enhances macrophagic proliferation via disturbing fatty acid profiles and oxidative phosphorylation in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic pathology, leading to acute coronary heart disease or stroke. MiR-127 has been found significantly upregulated in advanced atherosclerosis. But its function in atherosclerosis remains unexplored. We explored the role of miR-127-3p in regulating atherosclerosis development and its downstream mechanisms. METHODS: The expression profile of miR-127 in carotid atherosclerotic plaques of 23 patients with severe carotid stenosis was detected by RT-qPCR and in situ hybridization. Primary bone marrow-derived macrophages (BMDM) stimulated with oxidized low-density lipoprotein were used as an in vitro model. CCK-8, EdU, RT-qPCR, and flow cytometry were used to detect the proliferative capacity and polarization of BMDM, which were infected by lentivirus-carrying plasmid to upregulate or downregulate miR-127-3p expression, respectively. RNA sequencing combined with bioinformatic analysis and targeted fatty acid metabolomics approach were used to detect the transcriptome and lipid metabolites. The association between miR-127-3p and its target was verified by dual-luciferase activity reporting and Western blotting. Oxygen consumption rate of BMDM were detected using seahorse analysis. High-cholesterol-diet-fed low density lipoprotein deficient (LDLR-/-) mice, with-or-without carotid tandem-stenosis surgery, were treated with miR-127-3p agomir or antagomir to examine its effect on plaque development and stability. RESULTS: miR-127-3p, not -5p, is elevated in human advanced carotid atheroma and its expression is positively associated with macrophage accummulation in plaques. In vitro, miR-127-3p-overexpressed macrophage exhibites increased proliferation capacity and facilitates M1 polariztion whereas the contrary trend is present in miR-127-3p-inhibited macrophage. Stearoyl-CoA desaturase-1 (SCD1) is one potential target of miR-127-3p. miR-127-3p mimics decreases the activity of 3' untranslated regions of SCD-1. Furthermore, miR-127-3p downregulates SCD1 expression, and reversing the expression of SCD1 attenuates the increased proliferation induced by miR-127-3p overexpression in macrophage. miR-127-3p overexpression could also lead to decreased content of unsaturated fatty acids (UFAs), increased content of acetyl CoA and increased level of oxidative phosphorylation. In vivo, miR-127-3p agomir significantly increases atherosclerosis progression, macrophage proliferation and decreases SCD1 expression and the content of UFAs in aortic plaques of LDLR-/- mice. Conversely, miR-127-3p antagomir attenuated atherosclerosis, macrophage proliferation in LDLR-/- mice, and enhanced carotid plaque stability in mice with vulnerable plaque induced. CONCLUSION: MiR-127-3p enhances proliferation in macrophages through downregulating SCD-1 expression and decreasing the content of unsaturated fatty acid, thereby promoting atherosclerosis development and decreasing plaque stability. miR-127-3p/SCD1/UFAs might provide potential therapeutic target for anti-inflammation and atherosclerosis.

Age and BMI have different effects on subcutaneous, visceral, liver, bone marrow, and muscle adiposity, as measured by CT and MRI.

OBJECTIVE: We analyzed quantitative computed tomography (CT) and chemical shift-encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots. METHODS: In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2-L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements. RESULTS: Of the 168 men, 29% had normal BMI (<24.0 kg/m2), 47% had overweight (24.0-27.9 kg/m2), and 24% had obesity (≥ 28.0 kg/m2). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes. CONCLUSIONS: Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT.

Inter-rater variability and repeatability in the assessment of the Tanner-Whitehouse classification of hand radiographs for the estimation of bone age.

OBJECTIVE: To determine which bones and which grades had the highest inter-rater variability when employing the Tanner-Whitehouse (T-W) method. MATERIALS AND METHODS: Twenty-four radiologists were recruited and trained in the T-W classification of skeletal development. The consistency and skill of the radiologists in determining bone development status were assessed using 20 pediatric hand radiographs of children aged 1 to 18 years old. Four radiologists had a poor concordance rate and were excluded. The remaining 20 radiologists undertook a repeat reading of the radiographs, and their results were analyzed by comparing them with the mean assessment of two senior experts as the reference standard. Concordance rate, scoring, and Kendall's W were calculated to evaluate accuracy and consistency. RESULTS: Both the radius, ulna, and short finger (RUS) system (Kendall's W = 0.833) and the carpal (C) system (Kendall's W = 0.944) had excellent consistency, with the RUS system outperforming the C system in terms of scores. The repeatability analysis showed that the second rating test, performed after 2 months of further bone age assessment (BAA) practice, was more consistent and accurate than the first. The capitate had the lowest average concordance rate and scoring, as well as the lowest overall concordance rate for its D classification. Moreover, the G classifications of the seven carpal bones all had a concordance rate less than 0.6. The bones with lower Kendall's W were likewise those with lower scores and concordance rates. CONCLUSION: The D grade of the capitate showed the highest variation, and the use of the Tanner-Whitehouse 3rd edition (T-W3) to determine bone age (BA) was frequently inconsistent. A more comprehensive description with a focus on inaccuracy bones or ratings and a modification to the T-W3 approach would significantly advance BAA.

Reference Values for Paravertebral Muscle Size and Myosteatosis in Chinese Adults, a Nationwide Multicenter Study.

RATIONALE AND OBJECTIVES: The paravertebral muscles, characterized by their susceptibility to severe size loss and fat infiltration in old age, lack established reference values for age-related variations in muscle parameters. This study aims to fill this gap by establishing reference values for paravertebral muscles in a Chinese adult population. MATERIALS AND METHODS: This cross-sectional study utilized the baseline data from the prospective cohort China Action on Spine and Hip (CASH). A total of 4305 community-dwelling participants aged 21-80 years in China were recruited between 2013 and 2017. Pregnant women, individuals with metal implants, limited mobility or diseases/conditions (spinal tumor, infection, etc.) affecting lumbar vertebra were excluded from the study. Psoas and paraspinal muscles were measured in quantitative computed tomography (QCT) images at the L3 and L5 levels using Osirix software. Age-related reference values for muscle area, density, and fat fraction were constructed as percentile charts using the lambda-mu-sigma (LMS) method. RESULTS: The paravertebral muscles exhibited an age-related decline in muscle area and density, coupled with an increase in muscle fat fraction. Between the ages of 25 and 75, the reductions in psoas and paraspinal muscle cross-sectional area at the L3 level were - 0.47%/yr and - 0.53%/yr in men, and - 0.19%/yr and - 0.23%/yr in women, respectively. Notably, accelerated muscle loss was observed during menopause and postmenopause in women (45-75 years) and intermittently during middle and old age in men (35-55 and 60-75 years). Besides, the age-related decreases in PSMA, PMA, and PSMD and the increases in PSMFF were more pronounced in L5 than in L3 CONCLUSION: This study shows distinct patterns of accelerated muscle loss were identified in menopausal and postmenopausal women and in middle-aged and old men. The findings contribute valuable information for future investigations on paravertebral muscle loss and myosteatosis.

A thermostable xylanase hydrolyzes several polysaccharides from Bacillus altitudinis JYY-02 showing promise for industrial applications.

Polysaccharides have attracted immense attention as the largest source of bioactive compounds. Its bioavailability and bioactivity can be improved by utilizing degradation enzymes to reduce their molecular weight and viscosity. In this study, a 654 bp gene encoding xylanase was screened from the genome of Bacillus altitudinis JYY-02 and overexpressed in Escherichia coli Rosetta (DE3). The recombinant xylanase with a molecular weight of 27.98 kDa was purified (11.7-fold) using Ni-NTA affinity chromatography, with a 43.6% final yield. Through molecular docking, Glu, Arg, Tyr, and Trp were found to be the main amino acids involved in the interaction between xylanase and xylobiose. The effects of pH, temperature, metal ions, and substrates on xylanase activity were determined, and the results showed that the highest catalytic activity was displayed at pH 6.5, 50 °C temperature, with Cu2+ as an activator and xylan as the substrate. The Km (substrate concentration that yields a half-maximal velocity) and Vmax (maximum velocity) of recombinant xylanase were 6.876 mg/mL and 10984.183 µmol/mg∙pr/min, respectively. The recombinant xylanase was thermostable, with 85% and 39% of the enzymatic activity retained after 1 h at 60 °C and 1 h at 90 °C, respectively. The recombinant xylanase demonstrated a significant clarifying effect on fruit juices.

Comparisons of Hounsfield units and volumetric bone density in discriminating vertebral fractures on lumbar CT scans.

OBJECTIVES: To compare the performance of areal Hounsfield units (aHUs), volumetric Hounsfield units (vHUs), and volumetric bone mineral density (vBMD) by quantitative CT (QCT) in discriminating vertebral fractures (VFs) risk. METHODS: We retrospectively included CT scans of the lumbar spine 101 VFs cases (60 women, mean age: 64 ± 4 years; 41 men, mean age: 73 ± 10 years) and sex- and age-matched 101 control subjects (60 women, mean age: 64 ± 4 years; 41 men, mean age: 72 ± 7 years). In order to assess the discriminatory capability of aHU, vHU, and vBMD measurements at the L1 and L2 levels in identifying VFs, we conducted binary logistic regression and receiver operating characteristic (ROC) curve analyses in men and women. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: In both men and women with and without VFs, aHU, vHU, and vBMD were highly correlated with each other (r2 from 0.832 to 0.957, all P < .001). There was a statistically significant difference in aHU, vHU, and vBMD between subjects with and without VFs (P < .001). When age, gender, and BMI were taken into account as covariances and adjusted simultaneously, odds ratios (ORs) for aHU, vHU, and vBMD values, which represent the risk of VFs, were significant (P < .001). Compared with aHU and vHU, vBMD was more strongly associated with VF risk (vBMD: OR, 6.29; 95% CI, 3.83-10.35 vs vHU: OR, 3.64; 95% CI, 2.43-5.46 vs aHU: OR, 2.56; 95% CI, 1.79-3.67). In both men and women, further, vBMD had higher values for AUC, sensitivity, specificity, PPV, and NPV compared to vHU, with vHU in turn surpassing aHU. The area under the receiver operating characteristic curve (AUC) for discriminating VFs using the average aHU, vHU, and vBMD of 2 vertebrae was 0.72, 0.77, and 0.87 in men and 0.76, 0.79, and 0.86 in women. In both men and women, there exist statistically significant differences in the AUC when employing the 3 measurements-namely, aHU, vHU, and vBMD-to discriminate fractures (P < .05). CONCLUSIONS: The QCT-measured vBMD is more associated with acute VFs than vHU and aHU values of the lumbar spine. Although the use of vHU and aHU values for the diagnosis of osteoporosis and discriminating fracture risk is limited to scanner- and imaging protocol-specific, they have great potential for opportunistic osteoporosis screening, particularly vHU. ADVANCES IN KNOWLEDGE: The novelty of this study presents a comparison of the VF discriminative capabilities among aHU, vHU, and vBMD. The vHU values introduced in this study demonstrate a greater capacity to discriminate fractures compared to aHU, presenting an improved clinical choice. Although its discriminatory capability is slightly lower than that of vBMD, it is more convenient to measure and does not require specialized software.

METTL3-mediated m6A modification of NORAD inhibits the ferroptosis of vascular smooth muscle cells to attenuate the aortic dissection progression in an YTHDF2-dependent manner.

Ferroptosis of vascular smooth muscle cells (VSMCs) is related to the incidence of aortic dissection (AD). Long non-coding RNA (lncRNA) NORAD plays a crucial role in the progression of various diseases. The present study aimed to investigate the effects of NORAD on the ferroptosis of VSMCs and the molecular mechanisms. The expression of NORAD, HUR, and GPX4 was detected using quantitative real-time PCR (qPCR) or western blot. Ferroptosis was evaluated by detecting lactate dehydrogenase (LDH) activity, lipid reactive oxygen species (ROS), malonaldehyde (MDA) content, L-Glutathione (GSH) level, Fe2+ content, and ferroptosis-related protein levels. The molecular mechanism was assessed using RNA pull-down, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. The histology of aortic tissues was assessed using H&E, elastic Verhoeff-Van Gieson (EVG), and Masson staining assays. The data indicated that NORAD was downregulated in patients with AD and AngII-treated VSMCs. Overexpression of NORAD promoted VSMC growth and inhibited the ferroptosis induced by AngII. Mechanistically, NORAD interacted with HUR, which promoted GPX4 mRNA stability and elevated GPX4 levels. Knockdown of GPX4 abrogated the effects of NORAD on cell growth and ferroptosis of AngII-treated VSMCs. Moreover, METTL3 promoted m6A methylation of NORAD in an YTHDF2-dependent manner. In addition, NORAD attenuated AAD symptoms, incidence, histopathology, inflammation, and ferroptosis in AAD mice. In conclusion, METTL3-mediated NORAD inhibited ferroptosis of VSMCs via the HUR/GPX4 axis and decelerated AAD progression, suggesting that NORAD may be an AD therapeutic target.

Risk prediction of second hip fracture by bone and muscle density of the hip varies with time after first hip fracture: A prospective cohort study.

Purpose: Predictors of 'imminent' risk of second hip fracture are unknown. The aims of the study were to explore strength of hip areal bone mineral density (aBMD), and muscle area and density for predicting second hip fracture at different time intervals. Methods: Data of the Chinese Second Hip Fracture Evaluation were analyzed, a longitudinal study to evaluate the risk of second hip fracture (of the contralateral hip) by using CT images obtained immediately after first hip fracture. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur at the contralateral unfractured side. Patients were followed up for a median time of 4.5 years. Separate Cox models were used to predict second hip fracture risk at different time intervals after first event adjusted for age, sex, BMI and diabetes. Results: The mean age of subjects with imminent (within 1st or 2nd year) second hip fracture was 79.80 ± 5.16 and 81.56 ± 3.64 years. In the 1st year after the first hip fracture, femoral neck (FN) aBMD predicted second hip fracture (HR 5.88; 95 % CI, 1.32-26.09). In the remaining years of follow-up after 2nd year, muscle density predicted second hip fracture (G.MaxM HR 2.13; 95 % CI, 1.25-3.65,G.Med/MinM HR 2.10; 95 % CI, 1.32-3.34). Conclusions: Our results show that femoral neck aBMD is an important predictor for second hip fracture within the first year and therefore suggest supports the importance concept of early and rapid-acting bone-active drugs to increase hip BMD. In addition, the importance of muscle density predicting second hip fracture after the second year suggest post hip fracture rehabilitation and exercise programs could also be important to reduce muscle fatty infiltration.

External validation of a convolutional neural network algorithm for opportunistically detecting vertebral fractures in routine CT scans.

The Convolutional Neural Network algorithm achieved a sensitivity of 94% and specificity of 93% in identifying scans with vertebral fractures (VFs). The external validation results suggest that the algorithm provides an opportunity to aid radiologists with the early identification of VFs in routine CT scans of abdomen and chest. PURPOSE: To evaluate the performance of a previously trained Convolutional Neural Network (CNN) model to automatically detect vertebral fractures (VFs) in CT scans in an external validation cohort. METHODS: Two Chinese studies and clinical data were used to retrospectively select CT scans of the chest, abdomen and thoracolumbar spine in men and women aged ≥50 years. The CT scans were assessed using the semiquantitative (SQ) Genant classification for prevalent VFs in a process blinded to clinical information. The performance of the CNN model was evaluated against reference standard readings by the area under the receiver operating characteristics curve (AUROC), accuracy, Cohen's kappa, sensitivity, and specificity. RESULTS: A total of 4,810 subjects were included, with a median age of 62 years (IQR 56-67), of which 2,654 (55.2%) were females. The scans were acquired between January 2013 and January 2019 on 16 different CT scanners from three different manufacturers. 2,773 (57.7%) were abdominal CTs. A total of 628 scans (13.1%) had ≥1 VF (grade 2-3), representing 899 fractured vertebrae out of a total of 48,584 (1.9%) visualized vertebral bodies. The CNN's performance in identifying scans with ≥1 moderate or severe fractures achieved an AUROC of 0.94 (95% CI: 0.93-0.95), accuracy of 93% (95% CI: 93%-94%), kappa of 0.75 (95% CI: 0.72-0.77), a sensitivity of 94% (95% CI: 92-96%) and a specificity of 93% (95% CI: 93-94%). CONCLUSION: The algorithm demonstrated excellent performance in the identification of vertebral fractures in a cohort of chest and abdominal CT scans of Chinese patients ≥50 years.

Automated Segmentation and Classification of Knee Synovitis Based on MRI Using Deep Learning.

OBJECTIVES: To develop a deep learning (DL) model for segmentation of the suprapatellar capsule (SC) and infrapatellar fat pad (IPFP) based on sagittal proton density-weighted images and to distinguish between three common types of knee synovitis. MATERIALS AND METHODS: This retrospective study included 376 consecutive patients with pathologically confirmed knee synovitis (rheumatoid arthritis, gouty arthritis, and pigmented villonodular synovitis) from two institutions. A semantic segmentation model was trained on manually annotated sagittal proton density-weighted images. The segmentation results of the regions of interest and patients' sex and age were used to classify knee synovitis after feature processing. Classification by the DL method was compared to the classification performed by radiologists. RESULTS: Data of the 376 patients (mean age, 42 ± 15 years; 216 men) were separated into a training set (n = 233), an internal test set (n = 93), and an external test set (n = 50). The automated segmentation model showed good performance (mean accuracy: 0.99 and 0.99 in the internal and external test sets). On the internal test set, the DL model performed better than the senior radiologist (accuracy: 0.86 vs. 0.79; area under the curve [AUC]: 0.83 vs. 0.79). On the external test set, the DL diagnostic model based on automatic segmentation performed as well or better than senior and junior radiologists (accuracy: 0.79 vs. 0.79 vs. 0.73; AUC: 0.76 vs. 0.77 vs. 0.70). CONCLUSION: DL models for segmentation of SC and IPFD can accurately classify knee synovitis and aid radiologic diagnosis.

Epitranscriptome analysis of NAD-capped RNA by spike-in-based normalization and prediction of chronological age.

Nicotinamide adenine dinucleotide (NAD) can be used as an initiating nucleotide in RNA transcription to produce NAD-capped RNA (NAD-RNA). RNA modification by NAD that links metabolite with expressed transcript is a poorly studied epitranscriptomic modification. Current NAD-RNA profiling methods involve multi-steps of chemo-enzymatic labeling and affinity-based enrichment, thus presenting a critical analytical challenge to remove unwanted variations, particularly batch effects. Here, we propose a computational framework, enONE, to remove unwanted variations. We demonstrate that designed spike-in RNA, together with modular normalization procedures and evaluation metrics, can mitigate technical noise, empowering quantitative and comparative assessment of NAD-RNA across different datasets. Using enONE and a human aging cohort, we reveal age-associated features of NAD-capping and further develop an accurate RNA-based aging clock that combines signatures from both transcriptome and NAD-modified epitranscriptome. enONE facilitates the discovery of NAD-RNA responsive to physiological changes, laying an important foundation for functional investigations into this modification.

Associations of Quantitative and Qualitative Muscle Parameters With Second Hip Fracture Risk in Older Women: A Prospective Cohort Study.

Older women with a first hip fracture exhibit heightened susceptibility and incidence of second fracture and potentially severe consequences. This prospective study was to compare the predictive power of qualitative and quantitative muscle parameters for a second hip fracture in older women with a first hip fracture. A total of 206 subjects were recruited from the longitudinal Chinese Second Hip Fracture Evaluation study. Hip computed tomography (CT) scans were obtained immediately after the first fracture. Muscle fat infiltration was assessed according to the Goutallier classification qualitatively. Quantitative parameters included cross-sectional area and density of gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) muscles. CT X-ray absorptiometry was used to measure the areal bone mineral density (aBMD) of the contralateral femur. Cox proportional hazards models were used to compute hazard ratios (HR) of second hip fracture risk. The mean age of subjects was 74.9 (±9.5) years at baseline. After 4.5 years, 35 had a second hip fracture, 153 without a second hip fracture, and 18 died. Except for the combined G.MinM Goutallier grade 3 and 4 groups before adjustment for covariates (HR = 5.83; 95% confidence interval [CI] 1.49-22.83), there were no significant HRs for qualitative classification to predict a second hip fracture. Among quantitative metrics, after adjustment for covariates, G.Med/MinM density was significant in the original (HR = 1.44; CI 1.02-2.04) and competing risk analyses (HR = 1.46; CI 1.02-2.07). After additional adjustment for femoral neck (FN) aBMD, G.Med/MinM density remained borderline significant for predicting a second hip fracture in competing risk analysis (HR = 1.43; CI 0.99-2.06; p = 0.057). Our study revealed that Goutallier classification was less effective than quantitative muscle metrics for predicting hip second fracture in this elderly female cohort. After adjustment for FN aBMD, G.Med/MinM density is a borderline independent predictor of second hip fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Impact of Mn Alloying on Phase Stabilities, Magnetic Properties and Electronic Structures in Fe.

Impacts of Mn alloying on lattice stabilities, magnetic properties, electronic structures of the bcc and fcc phases and the fcc→bcc phase transition in Fe16-xMnx (x = 0, 1 and 2) alloys are studied by first-principles calculations. Results show that the doped Mn atom prefers ferromagnetic and antiferromagnetic interaction with the host Fe atoms in the bcc and fcc phases, respectively. In these two phases, the magnetic moment of Mn is smaller and larger than Fe, respectively. The local moment of Fe is decided by the Fe-Mn distance in the bcc phase, whereas in the fcc phase, it is determined by spatial orientation with Mn. In the different phases, Mn prefers different site occupations, which can be understood from the electronic density of states near Fermi energy, implying a possibility of element redistribution during phase transition. The driving force of phase transition decreases with Mn alloying. Both destabilized bcc phase and stabilized fcc phase contribute to the inhibited phase transition, but the latter plays a dominant role. Antiferromagnetism is recognized as the key reason for the enhanced stability of the fcc phase by Mn alloying.

Deep Learning-Based Fully Automated Segmentation of Regional Muscle Volume and Spatial Intermuscular Fat Using CT.

RATIONALE AND OBJECTIVES: We aim to develop a CT-based deep learning (DL) system for fully automatic segmentation of regional muscle volume and measurement of the spatial intermuscular fat distribution of the gluteus maximus muscle. MATERIALS AND METHODS: A total of 472 subjects were enrolled and randomly assigned to one of three groups: a training set, test set 1, and test set 2. For each subject in the training set and test set 1, we selected six slices of the CT images as the region of interest for manual segmentation by a radiologist. For each subject in test set 2, we selected all slices of the gluteus maximus muscle on the CT images for manual segmentation. The DL system was constructed using Attention U-Net and the Otsu binary thresholding method to segment the muscle and measure the fat fraction of the gluteus maximus muscle. The segmentation results of the DL system were evaluated using the Dice similarity coefficient (DSC), Hausdorff distance (HD), and the average surface distance (ASD) as metrics. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess agreement in the measurements of fat fraction between the radiologist and the DL system. RESULTS: The DL system showed good segmentation performance on the two test sets, with DSCs of 0.930 and 0.873, respectively. The fat fraction of the gluteus maximus muscle measured by the DL system was in agreement with the radiologist (ICC=0.748). CONCLUSION: The proposed DL system showed accurate, fully automated segmentation performance and good agreement with the radiologist at fat fraction evaluation, and can be further used for muscle evaluation.