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Abstract Late complications of radiotherapy can include a variety of issues, such as xerostomia, dysphagia, taste changes, digestive and absorption dysfunction. These late complications can seriously impact the nutritional status and quality of life of patients following radiotherapy, and may even adversely affect tumor control and patient survival. Comprehensive nutritional management strategies should be implemented to address these late complications. For radiation-induced xerostomia, salivary stimulant drugs, saliva substitutes, and hyperbaric oxygen therapy have demonstrated efficacy in alleviating dry mouth symptoms. The management of post-radiation trismus remains challenging, with functional training, including active jaw exercises, passive motor devices, and splints, being the primary interventions. In the case of radiation-induced dysphagia, a multidisciplinary team approach is recommended, incorporating malnutrition risk assessment, personalized nutritional treatment, nursing care, rehabilitation training, and patient education. Protecting normal organs, such as the tongue and oral cavity, during radiotherapy planning can help prevent and mitigate taste changes, which can be further managed with zinc supplements, oral care, and lactoferrin supplementation. For post-radiation digestive and absorption dysfunction, a comprehensive assessment of the patient's nutritional status, site of gastrointestinal injury, and potential complications (e.g., bleeding, perforation) is crucial in guiding the selection of appropriate nutritional support, ranging from enteral nutrition as the first-line approach to supplemental or even exclusive parenteral nutrition. Surgical intervention may be necessary in some cases. By implementing these multifaceted nutritional management strategies, healthcare professionals can optimize the care of cancer patients undergoing radiotherapy and mitigate the adverse impact of late radiation complications on their overall well-being and treatment outcomes.

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/β ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

Magnetic resonance–guided adaptive radiotherapy (MRgART) represents the latest frontier in precision radiotherapy. It is distinguished from other modalities by the possibility of acquiring high-contrast soft tissue images, combined with the ability to recalculate and re-optimize the plan on the daily anatomy. The extensive database of available images offers ample scope for using disciplines such as radiomics to try to correlate features and outcomes. This study aimed to correlate the change of radiomics feature along the treatment to pathological complete response (pCR) for locally advanced rectal cancer (LARC) patients. Twenty-eight LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT) with a short course (25 Gy, 5 Gy × 5f) MRgART at 1.5 Tesla MR-Linac were enrolled. The T2-weighted images acquired at each fraction, corresponding target delineation, pCR result of the surgical specimen, and clinical variables were collected. Seven families of features [First Order, Shape, Gray-level Co-occurrence Matrix (GLCM), Gray-level Dependence Matrix (GLDM), Gray-level Run Length Matrix (GLRLM), Gray-level Size Zone Matrix (GLSZM), and Neighborhood Gray Tone Difference Matrix (NGTDM)] were extracted, and delta features were calculated from the ratio of features of each successive fraction to those of the first fraction. Mann-Whitney U test and LASSO were utilized to reduce the dimension of features and select those features that are most significant to pCR. At last, the radiomics signatures were established by linear regression with the final set of features and their coefficients. A total of 581 radiomics features were extracted, and 2,324 delta features were calculated for each patient. Nineteen features and delta features, and one clinical variable (cN) were significant (p< 0.05) to pCR; seven predictive features were further selected and included in the linear regression to construct the radiomics signature significantly discriminating pCR and non-pCR groups (p< 0.05). Delta features based on MRI images acquired during a short course MRgART could potentially be used to predict treatment response in LARC patients undergoing nCRT.

Background and purpose: Neoadjuvant Chemotherapy (NAC) followed by concurrent chemoradiotherapy (CCRT) is promising in improving the survival rate for advanced nasopharyngeal carcinoma (NPC) patients relative to CCRT alone. However, not all patients respond well to NAC. Therefore, we aimed to develop and evaluate a modified radiomics model for the NAC response prognosis in NPC patients. Methods: A total of 165 patients with biopsy-proven locally advanced NPC were retrospectively selected from the database of our hospital. 85 out of them were for training and cross-validation, while the other 80 patients were for independent testing. All patients were treated with NAC and underwent MRI inspection, including T1-weighted (T1), T2-weighted (T2), and contrast-enhanced T1-weighted (T1-cs) sequences before and after two cycles of NAC. We classified the patients into the response or non-response groups by the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Radiomics features were extracted from the primary and lymph node gross tumor volume in each sequence. To further improve the predictive performance, the permutation of multiple combinations of extraction parameters has first ever been investigated in the NAC prognosis for NPC patients. The model was constructed by logistic regression and cross-validated by bootstrapping with a resampling number of 1000. Independent testing was also implemented. In addition, we also applied an imbalance-adjusted bootstrap strategy to decrease the bias of small samples. Results: For the cross-validation cohort, the resultant AUC, sensitivity, and specificity in terms of 95% confidence interval were 0.948 ± 0.004, 0.849 ± 0.005, and 0.840 ± 0.010. For the independent testing cohort, the model reached an AUC of 0.925, a sensitivity of 0.821, and a specificity of 0.792. There was a significant difference in the estimated radiomics score between the response and non-response groups (P

ObjectivesIt remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy.MethodsWe retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student’s t-test or Mann–Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia.ResultsAmong the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups.ConclusionSarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.

ObjectivesAlthough lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass.Materials and methodsWe conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients’ serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan–Meier curves and a Cox proportional hazards model.ResultsOf the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3–92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37–0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels.ConclusionPost-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.

Abstract Lower back pain comprises the majority of the disease burden of patients with ankylosing spondylitis (AS), while the alterations of the large-scale brain networks could be implicated in the neuropathophysiology of pain. The frontoparietal network (FPN) is known as a pain modulation hub, with key nodes dorsolateral prefrontal cortex (dlPFC) and ventrolateral prefrontal cortex (vlPFC) participating in the pain modulation and reappraisal process. In this study, we adopted the analytical approaches of independent component analysis (ICA) and seed-based correlation analysis (SCA) to examine the resting-state functional connectivity (rsFC) of the large-scale brain networks, notably FPN, between 82 AS patients and 61 healthy controls (HCs). We also investigated the correlation between the rsFC and the clinical measures of AS patients. Both ICA and SCA consistently showed that the rsFC between FPN and mPFC, a key node of the default mode network (DMN), was significantly increased in AS. In addition, SCA also identified a cluster at the right posterior lobe of cerebellum which exhibited increased rsFC with the posterior cingulate cortex, and the right lateral prefrontal cortex also showed increased rsFC with the right dlPFC. Correlation analysis showed that the rsFC between mPFC and the left anterior prefrontal cortex was significantly correlated with C-reactive protein in AS. The increased FPN-DMN connectivity could contribute to the neuropathophysiology of lower back pain in AS, with potential association with faulty pain modulation and reappraisal mechanisms facilitated by the FPN.

Abstract Fibromyalgia (FM) and ankylosing spondylitis (AS) are both rheumatic diseases characterized by significant musculoskeletal pain. In this study, we investigated the differences of the resting-state network (RSN) connectivity and gray matter volume (GMV) between FM, AS and healthy controls (HCs). We recruited 38 FM patients, 82 AS patients and 61 HCs in this study. All the participants underwent resting-state functional MRI (rs-fMRI) scans in a GE 3.0T MR system. Independent component analysis (ICA) was conducted on the rs-fMRI data, and group differences of the rsFC between different resting-state networks were calculated using dual regression. We also conducted voxel-based morphometry (VBM) analysis to investigate the differences of the GMV in FM, AS and HCs. The rsFC between the dorsal default mode network (DDMN) and the body of left caudate nucleus was significantly decreased in FM patients in comparison to AS patients (87 voxels, p = 0.025). VBM analysis showed that the GMV of the left posterior lobe of cerebellum was significantly increased in FM patients compared with AS patients (88 voxels, p = 0.036). Neither ICA nor VBM analysis revealed significant differences of RSN connectivity or GMV between FM patients and HCs. The altered rsFC between DMN and the caudate nucleus suggested an aberrant cortico-striato-thalamo-cortical circuit in FM patients, indicating aberrant reward processing, with potential association with mood, motivation and cognitive functions. The increased GMV in the left posterior lobe of cerebellum indicated the participation of cerebellum in the abnormal pain processing in FM patients.

Abstract Background This study aimed to investigate the accuracy of identifying enthesitis along with other inflammatory lesions and structural lesions on the MRI of the sacroiliac joints (SIJ) by readers of varying experience and how training sessions and workshops could help improve the accuracy. Methods A total of 224 patients with clinical diagnosis of axial spondyloarthritis who underwent SIJ MRI examinations were retrospectively included in this study. Three readers with 5 years, 3 years and 1 year of experience in musculoskeletal imaging were invited to review the SIJ MRI images independently, while the imaging reports of a senior radiologist (> 10 years’ experience) were used as reference. After the first round of image review, a training session and a workshop on the imaging of SIJ in spondyloarthritis were held and the three readers were asked to review the images in the second round. We calculated the accuracy of identifying inflammatory and structural lesions of the three readers as well as the intra-reader agreement. Results Enthesitis could be observed in 52.23% of the axial spondyloarthritis patients, while 81.58% of the patients with enthesitis were accompanied with bone marrow edema. All the three readers showed better accuracy at identifying structural lesions than inflammatory lesions. In the first round of image review, the three readers only correctly identified 15.07%, 2.94% and 0.74% of the enthesitis sites. After the training session and workshop, the accuracy rose to 61.03%, 39.34% and 20.22%. The intra-reader agreement of enthesitis calculated as Cohen’s kappa was 0.23, 0.034 and 0.014, respectively. Conclusion Readers with less experience in musculoskeletal imaging showed lower accuracy of identifying inflammatory lesions, notably enthesitis. Training sessions and workshops could help improve the diagnostic accuracy of the junior readers.

Acidic soils cover approximately 50 % of the arable land with high N2O emission potential. 3,4-dimethylpyrazole phosphate (DMPP) inhibits N2O emission from soils; however, its efficiency is affected by acidity. Liming is used for soil conditioning to ameliorate the effects of acidity. In the present study, we investigated the effects of liming on the efficiency of DMPP in inhibiting N2O emission in acidic soils and the mechanisms involved. We evaluated the impact of liming, DMPP, and combined application and its microbial responses in two acidic soils from Zengcheng (ZC) and Shaoguan (SG) City, Guangdong Province, China. Soils were subjected to four treatments: un-limed soil (low soil pH) + urea (LU), un-limed soil + urea + DMPP (LD), limed soil (high soil pH) + urea (HU), and limed soil + urea + DMPP (HD) for analyses of the mineral N, N2O emissions, and full-length 16S and metagenome sequencing. The results revealed that, HU significantly decreased and increased the N2O emission by 17.8 % and 235.0 % in ZC and SG, respectively, compared with LU. This was caused by a trade-off between N2O production and consumption after liming, where microbial communities and N-cycling functional genes show various compositions in different acidic soils. LD reduced N2O emission by 23.5 % in ZC, whereas decreased 1.5 % was observed in SG. Interestingly, DMPP efficiency considerably improved after liming in two acidic soils. Compared with LU, HD significantly reduced N2O emissions by 61.2 % and 48.5 % in ZC and SG, respectively. Synergy of mitigation efficiency was observed by lime and DMPP application, which was attributed to the changes in the dominant nitrifiers and the increase in N2O consumption by denitrifiers. The combined application of lime and DMPP is a high-efficiency strategy for N2O mitigation can ensure agricultural sustainability in acidic arable soils with minimal environmental damage.

BackgroundFindings of fatty lesions in the context of other imaging manifestations, especially bone marrow edema and erosions can effectively assist in the diagnosis of axSpA. Chemical shift-encoded MRI is a sequence which allows for the quantification of fat signal and has been applied in the imaging evaluation of the SIJ in axSpA. The objective of this study was to investigate the diagnostic performance of morphological features of fatty lesions visualized by CSE-MRI in the imaging evaluation of SIJ in axSpA.MethodsFatty lesions with morphological features (subchondral, homogeneity and distinct border) were assessed and recorded as a binary variable in each quadrant of the SIJ. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different morphological features as well as the anatomical distribution in patients with nr-axSpA and r-axSpA. T1-weighted images and CSE-MRI fat fraction maps were directly compared in the recognition of different morphological features.ResultsEighty-two patients [non-SpA (n = 21), nr-axSpA (n = 23), r-axSpA (n = 38)] with lower back pain (LBP) were enrolled. Presence of the three morphological features of fatty lesions had a specificity of 90.48% in axSpA. The sensitivities of being subchondral, homogeneity and distinct border were 52.17, 39.13 and 39.13% in nr-axSpA on T1-weighted images. For patients with r-axSpA, the sensitivities reached 86.84, 76.32 and 57.89%. No significant difference was found in the distribution of fatty lesions between T1-weighted images and CSE-MRI. However, CSE-MRI fat fraction maps could detect significantly more fatty lesions with homogeneity (p = 0.0412) and distinct border (p = 0.0159) than T1-weighted images in the sacroiliac joint, but not subchondral lesions (p = 0.6831).ConclusionThe homogeneity and distinct border are more relevant for the diagnosis of axSpA. Moreover, CSE-MRI could detect more typical morphological features of fatty lesions than T1-weighted images in showing these two features. The presence of all three features was more likely to be indicative of axSpA.

Abstract Objective To construct a comprehensive simulation method of “gait-musculoskeletal system (MS)-finite element (FE)” for analysis of hip joint dynamics characteristics and the changes in the contact stress in the hip throughout a gait cycle. Methods Two healthy volunteers (male and female) were recruited. The 3D gait trajectories during normal walking and the CT images including the hip and femur of the volunteers were obtained. CT imaging data in the DICOM format were extracted for subjected 3D hip joint reconstruction. The reconstructed 3D model files were used to realize the subject-specific registration of the pelvis and thigh segment of general musculoskeletal model. The captured marker trajectory data were used to drive subject-specific musculoskeletal model to complete inverse dynamic analysis. Results of inverse dynamic analysis were exported and applied as boundary and load settings of the hip joint finite element in ABAQUS. Finally, the finite element analysis (FEA) was performed to analyze contact stress of hip joint during a gait cycle of left foot. Results In the inverse dynamic analysis, the dynamic changes of the main hip-femoral muscle force with respect to each phase of a single gait cycle were plotted. The hip joint reaction force reached a maximum value of 2.9%BW (body weight) and appeared at the end of the terminal stance phase. Twin peaks appeared at the initial contact phase and the end of the terminal stance phase, respectively. FEA showed the temporal changes in contact stress in the acetabulum. In the visual stress cloud chart, the acetabular contact stress was mainly distributed in the dome of the acetabulum and in the anterolateral area at the top of the femoral head during a single gait cycle. The acetabular contact area was between 293.8 and 998.4 mm2, and the maximum contact area appear at the mid-stance phase or the loading response phase of gait. The maximum contact stress of the acetabulum reached 6.91 MPa for the model 1 and 6.92 MPa for the model 2 at the terminal stance phase. Conclusions The “Gait-MS-FE” technology is integrated to construct a comprehensive simulation framework. Based on human gait trajectories and their CT images, individualized simulation modeling can be achieved. Subject-specific gait in combination with an inverse dynamic analysis of the MS provides pre-processing parameters for FE simulation for more accurate biomechanical analysis of hip joint. Graphical abstract

BackgroundT1-weighted spoiled 3D Gradient Recalled Echo pulse sequences, exemplified by Liver Acquisition with Volume Acceleration-flexible MRI (LAVA-Flex), are currently the preferred MR sequence for detecting erosions of the sacroiliac joint (SIJ). However, zero echo time MRI (ZTE) is recently reported to provide excellent visualization of the cortical bone.PurposeTo directly compare the diagnostic accuracy of ZTE and LAVA-Flex in the detection of structural lesions of the SIJ, including erosions, sclerosis and joint space changes.Materials and methodsTwo readers independently reviewed the ldCT, ZTE and LAVA-Flex images of 53 patients diagnosed as axSpA and scored the erosions, sclerosis and joint space changes. Sensitivity, specificity and Cohen’s kappa (κ) of ZTE and LAVA-Flex were calculated, while McNemar’s test was employed to compare the two sequences for the positivity of detecting the structural lesions.ResultsAnalysis of diagnostic accuracy showed a higher sensitivity of ZTE in comparison with LAVA-Flex in the depiction of erosions (92.5% vs 81.5%, p

Bergamot (Citrus medica L. var. sarcodactylis) contains different bioactive compounds, and their effects remain unclear. Therefore, the structural and bio-function of bergamot dietary fiber were investigated. A sequential extraction procedure was utilized to obtain soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) from bergamot. The main monosaccharide in SDF and IDF is arabinose. SDF had a porous structure, which enhanced the water and oil holding capacity, as well as the cholesterol and glucose adsorption capacity, which was superior to that of IDF. In db/db diabetic mice, SDF and IDF regulated glucose tolerance and controlled blood glucose levels. Reduction of serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol in SDF and IDF could be observed. In summary, SDF and IDF from bergamot effectively promoted health in patients with diabetes.