Disparate Radiation-Induced Microstructural Injuries in Whole-Brain White Matter of Patients With Nasopharyngeal Carcinoma: A Longitudinal Study Using Multishell Diffusion MRI.

BACKGROUND: Evidence for prevention strategies of radiotherapy (RT)-related injury in patients with nasopharyngeal carcinoma (NPC) was lacking. Understanding the dynamic alterations in the cerebral white matter (WM) microstructure after RT may be helpful. PURPOSE: To investigate the dynamic alterations in the whole brain WM microstructure in patients with NPC in the 12 months after RT using multishell diffusion MRI (MS-dMRI). STUDY TYPE: Single-center longitudinal study. POPULATION: A total of 28 treatment-naïve patients with pathologically confirmed NPC (age: 39.68 ± 8.93 years, 11 female) and 20 healthy controls (age: 40.65 ± 9.76 years, 7 female). FIELD STRENGTH/SEQUENCES: A 3 T, MS-dMRI using a single-shot echo planar imaging sequence. ASSESSMENT: MS-dMRI was acquired at baseline for the NPC patients and healthy controls, at 0-3 (acute, AC), 6 (early delayed, ED) and 12 months (late delayed, LD) after RT for the NPC patients. The mean and maximum radiation doses to the temporal lobe were acquired. The quality of images was reviewed. MS-dMRI was analyzed using tract-based spatial statistics (TBSS). The presentations of injury were defined by the findings of TBSS. STATISTICAL TESTS: Chi-square, t tests, repeated ANOVA, and Spearman-rank correlation analysis were used. P < 0.05 was considered to be statistically significant. RESULTS: TBSS showed two WM injuries (injuries 1 and 2). Injury 1 emerged in the ED phase in the bilateral temporal poles and persisted throughout the ED and LD phases. Injury 2 developed from the AC to ED phase in the bilateral hemisphere and partially recovered in the LD phase. In the ED and LD phases, the multiple diffusion metrics were well correlated (r > 0.5 or <-0.5) with the RT dose, especially in the WM tracts in the temporal lobes. DATA CONCLUSION: Disparate WM injuries were observed in NPC patients after RT. The injuries may be primarily or secondarily induced by radiation. Injury 1 may be irreversible, while injury 2 seems to partially recover. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 4.

The network structure of mania symptoms differs between people with and without binge eating.

OBJECTIVES: People with bipolar disorder who also report binge eating have increased psychopathology and greater impairment than those without binge eating. Whether this co-occurrence is related to binge eating as a symptom or presents differently across full-syndrome eating disorders with binge eating is unclear. METHODS: We first compared networks of 13 lifetime mania symptoms in 34,226 participants from the United Kingdom's National Institute for Health and Care Research BioResource with (n = 12,104) and without (n = 22,122) lifetime binge eating. Second, in the subsample with binge eating, we compared networks of mania symptoms in participants with lifetime anorexia nervosa binge-eating/purging (n = 825), bulimia nervosa (n = 3737), and binge-eating disorder (n = 3648). RESULTS: People with binge eating endorsed every mania symptom significantly more often than those without binge eating. Within the subsample, people with bulimia nervosa most often had the highest endorsement rate of each mania symptom. We found significant differences in network parameter statistics, including network structure (M = 0.25, p = 0.001) and global strength (S = 1.84, p = 0.002) when comparing the binge eating with no binge-eating participants. However, network structure differences were sensitive to reductions in sample size and the greater density of the latter network was explained by the large proportion of participants (34%) without mania symptoms. The structure of the anorexia nervosa binge-eating/purging network differed from the bulimia nervosa network (M = 0.66, p = 0.001), but the result was unstable. CONCLUSIONS: Our results suggest that the presence and structure of mania symptoms may be more associated with binge eating as a symptom rather than any specific binge-type eating disorder. Further research with larger sample sizes is required to confirm our findings.

Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.

OBJECTIVE: The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic. METHOD: Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes. RESULTS: Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation. DISCUSSION: Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics. PUBLIC SIGNIFICANCE: In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.

Identification of environmental microorganism using optimally fine-tuned convolutional neural network.

To not only optimize the hyper-parameters of the classification layer of dense convolutional network with 201 convolutional layers (DenseNet-201) but also use data augmentation processes could enhance the performance of DenseNet-201, and DenseNet-201 is rarely applied to the identifications of the environmental microorganism (EM) images. Hence, this study was to propose the optimally fine-tuned DenseNet-201 (OFTD) with data augmentation to better classify the EM images on Environmental Microorganism Dataset (EMDS). The training dataset was composed of 70% Environmental Microorganism Dataset (EMDS) images and so was mainly used to fit the parameters of convolutional layers of optimally fine-tuned DenseNet-201 (OFTD). Meanwhile, the other EMDS images were considered as the testing dataset and used to qualify the performance of the OFTD. Also, gradient-weighted class activation mapping method (Grad-CAM) was adopted to visually illustrate the dominant features of the EM images. Based on the results, the OFTD model with data augmentation achieved the highest classification accuracy of 98.4%. In this case, so its stability and accuracy were guaranteed. Besides, the optimally fine-tuned classification layer is considered a more efficient method than the data augmentation technique adopted in this study when it comes to the improvement of the performance in DenseNet-201 implemented on EMDS. Grad-CAM highlighted the coarse EM features identified effectively by the OFTD; for example, foot and stalk were considered as the dominated features of Rotifera and Vorticella, respectively. In summary, the proposed OFTD with data augmentation could provide an efficient solution for the EM detection in digital microscope.

Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.

BACKGROUND: Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature. METHODS: Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n = 2890). RESULTS: Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR = 1.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR = 0.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR = 0.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR = 1.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios. CONCLUSION: Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.

Zfra Inhibits the TRAPPC6AΔ-Initiated Pathway of Neurodegeneration.

When WWOX is downregulated in middle age, aggregation of a protein cascade, including TRAPPC6AΔ (TPC6AΔ), TIAF1, and SH3GLB2, may start to occur, and the event lasts more than 30 years, which results in amyloid precursor protein (APP) degradation, amyloid beta (Aß) generation, and neurodegeneration, as shown in Alzheimer's disease (AD). Here, by treating neuroblastoma SK-N-SH cells with neurotoxin MPP+, upregulation and aggregation of TPC6AΔ, along with aggregation of TIAF1, SH3GLB2, Aß, and tau, occurred. MPP+ is an inducer of Parkinson's disease (PD), suggesting that TPC6AΔ is a common initiator for AD and PD pathogenesis. Zfra, a 31-amino-acid zinc finger-like WWOX-binding protein, is known to restore memory deficits in 9-month-old triple-transgenic (3xTg) mice by blocking the aggregation of TPC6AΔ, SH3GLB2, tau, and amyloid ß, as well as inflammatory NF-κB activation. The Zfra4-10 peptide exerted a strong potency in preventing memory loss during the aging of 3-month-old 3xTg mice up to 9 months, as determined by a novel object recognition task (ORT) and Morris water maize analysis. Compared to age-matched wild type mice, 11-month-old Wwox heterozygous mice exhibited memory loss, and this correlates with pT12-WWOX aggregation in the cortex. Together, aggregation of pT12-WWOX may link to TPC6AΔ aggregation for AD progression, with TPC6AΔ aggregation being a common initiator for AD and PD progression.

[Effect of Gegen Qinlian Decoction on cardiac diastolic function of diabetic mice with damp-heat syndrome].

This study was designed to explore the effect and mechanism of Gegen Qinlian Decoction(GQD) on cardiac function of diabetic mice with damp-heat syndrome. The db/db diabetic mice were exposed to the damp-heat environment test chamber for inducing the damp-heat syndrome. Forty-eight six-week-old db/db mice were randomly divided into six groups, namely the db/db diabetic model group, db/db diabetic mouse with damp-heat syndrome(db/db-dh) group, db/db diabetic mouse with damp-heat syndrome treated with low-dose GQD(db/db-dh+GQD-L) group, db/db-dh+GQD-M(medium-dose) group, db/db-dh+GQD-H(high-dose) group, and db/db-dh+lipro(liprostatin-1, the inhibitor of ferroptosis) group, with eight six-week-old db/m mice classified into the control group. The results showed that mice presented with the damp-heat syndrome after exposure to the "high-fat diet" and "damp-heat environment", manifested as the elevated fasting blood glucose, reduced food intake, low urine output, diarrhea, listlessness, loose and coarse hair, and dark yellow and lusterless fur. However, the intragastric administration of the high-dose GQD for 10 weeks ameliorated the above-mentioned symptoms, inhibited myocardial hypertrophy and fibrosis, and improved the cardiac diastolic function of db/db-dh mice. qPCR suggested that GQD regulated the expression of ferroptosis-related genes, weakened the lipid peroxidation in the myocardium, and up-regulated glutathione peroxidase 4(GPX4) expression in comparison with those in the db/db-dh group. At the same time, the ferroptosis inhibitor liprostatin-1 significantly improved the cardiac function and reversed the cardiac remodeling of db/db-dh mice. It can be concluded that the damp-heat syndrome may aggravate myocardial ferroptosis and accelerate cardiac remodeling of db/db mice, thus leading to diastolic dysfunction. GQD is able to improve cardiac remodeling and diastolic function in diabetic mice with damp-heat syndrome, which may be related to its inhibition of myocardial ferroptosis.

Research on Classification Model of Panax notoginseng Taproots Based on Machine Vision Feature Fusion.

The existing classification methods for Panax notoginseng taproots suffer from low accuracy, low efficiency, and poor stability. In this study, a classification model based on image feature fusion is established for Panax notoginseng taproots. The images of Panax notoginseng taproots collected in the experiment are preprocessed by Gaussian filtering, binarization, and morphological methods. Then, a total of 40 features are extracted, including size and shape features, HSV and RGB color features, and texture features. Through BP neural network, extreme learning machine (ELM), and support vector machine (SVM) models, the importance of color, texture, and fusion features for the classification of the main roots of Panax notoginseng is verified. Among the three models, the SVM model performs the best, achieving an accuracy of 92.037% on the prediction set. Next, iterative retaining information variables (IRIVs), variable iterative space shrinkage approach (VISSA), and stepwise regression analysis (SRA) are used to reduce the dimension of all the features. Finally, a traditional machine learning SVM model based on feature selection and a deep learning model based on semantic segmentation are established. With the model size of only 125 kb and the training time of 3.4 s, the IRIV-SVM model achieves an accuracy of 95.370% on the test set, so IRIV-SVM is selected as the main root classification model for Panax notoginseng. After being optimized by the gray wolf optimizer, the IRIV-GWO-SVM model achieves the highest classification accuracy of 98.704% on the test set. The study results of this paper provide a basis for developing online classification methods of Panax notoginseng with different grades in actual production.

Application of palladium-modified zeolite for prolonging post-harvest shelf life of banana.

BACKGROUND: The marketability of banana is limited by the rapid rate of ripening. However, the traditional post-harvest technologies may not be desirable. The aim of this study was to investigate the potential of a reusable material for the food preservation industry. RESULTS: The nanocomposite-based palladium (Pd)-modified zeolite (Pd/zeolite) was prepared by impregnating Pd into zeolite. Pd/zeolite had a Brunauer-Emmett-Teller dinitrogen specific surface area of 475 m2 g-1 with crystal structure similar to Y-zeolite. Transmission electron microscopy images showed the dispersion of Pd particles over the multi-pore zeolite support. Pd/zeolite uniquely acted as an adsorbent and a catalyst and was able to remove ethylene even after reaching breakthrough point. To prove Pd/zeolite is reusable, a 99 ± 0.8% ethylene removal efficiency still remained even after five consecutive cycles with repeated use of Pd/zeolite. The presence of Pd/zeolite significantly decreased the ethylene concentration during 18 days of storage at 20 ± 2 °C. CONCLUSIONS: Pd/zeolite could delay the ripening of banana and improve its firmness and the peel color significantly. Findings indicated that the as-prepared Pd/zeolite is an effective adsorbent/catalyst with high potential for practical application in ethylene removal, especially for the post-harvest period. © 2019 Society of Chemical Industry.

The intrinsically disordered N-terminal domain of galectin-3 dynamically mediates multisite self-association of the protein through fuzzy interactions.

Galectins are a family of lectins that bind ß-galactosides through their conserved carbohydrate recognition domain (CRD) and can induce aggregation with glycoproteins or glycolipids on the cell surface and thereby regulate cell activation, migration, adhesion, and signaling. Galectin-3 has an intrinsically disordered N-terminal domain and a canonical CRD. Unlike the other 14 known galectins in mammalian cells, which have dimeric or tandem-repeated CRDs enabling multivalency for various functions, galectin-3 is monomeric, and its functional multivalency therefore is somewhat of a mystery. Here, we used NMR spectroscopy, mutagenesis, small-angle X-ray scattering, and computational modeling to study the self-association-related multivalency of galectin-3 at the residue-specific level. We show that the disordered N-terminal domain (residues ∼20-100) interacts with itself and with a part of the CRD not involved in carbohydrate recognition (ß-strands 7-9; residues ∼200-220), forming a fuzzy complex via inter- and intramolecular interactions, mainly through hydrophobicity. These fuzzy interactions are characteristic of intrinsically disordered proteins to achieve liquid-liquid phase separation, and we demonstrated that galectin-3 can also undergo liquid-liquid phase separation. We propose that galectin-3 may achieve multivalency through this multisite self-association mechanism facilitated by fuzzy interactions.

Identification of urban park activity intensity at different thermal environments and visible sky by using sound levels.

An efficient urban environmental design considers appropriate thermal comfort condition, shaded space, and activity intensity. Physiologically equivalent temperature (PET) and visible sky, i.e., the sky view factor (SVF), are usually used as indicators to determine the outdoor thermal comfort and amount of shaded space, respectively. The activity intensity in urban parks, which is dependent on culture and micrometeorological conditions, was represented inappropriately by attendance density in Taiwan. To optimize the park design and improve the park utilization rate in Taiwan, several environmental factors such as sound pressure levels and numbers of park visitors were measured, and PET values and SVF values were calculated from primary micrometeorological data such as wind speed and globe temperature. This study proposed equivalent continuous sound pressure level (Leq) as a novel indicator to represent park activity intensity and investigated the correlation between Leq and SVF at different PET values. Leq was more appropriate than was attendance density in representing the park activity intensity in Taiwan. In addition, Leq was highly negatively correlated with SVF when visitors felt that the outdoor thermal comfort condition was hot or very hot. In other words, a lower degree of shading in the park resulted in lower activity intensity. Park visitors tended to engage in activities in the shaded regions because of more favorable thermal comfort conditions (i.e., neutral PET). The established quantitative relationships among Leq, PET, and SVF can serve as a reference for park planning.

Development of intelligent Municipal Solid waste Sorter for recyclables.

Sorting Municipal Solid Waste (MSW) has helped promote the awareness of sustainable development of environment. A robot equipped with an intelligent deep learning (DL) detection algorithm have been proposed to improve the sorting task. But most of the related studies aimed to better the DL algorithms on MSW detection, and few studies integrated the DL algorithms with a robot to identify the dominated factors to Intelligent MSW Sorter (IMSWS). Therefore, this study is to develop IMSWS prototype to better sort MSW, based on the pick-and-place process, and preliminarily evaluate the dominated factors. First, the delta robot prototype was manufactured, and IMSWS was performed with a camera to acquire the RGB image and the height of a MSW in the conveyor belt. The DL algorithm, YOLOv3 or YOLOv4, detected the type and plane location of the MSWs in the conveyor belt. Next, the sequence program transferred the valid MSW data to the delta robot. After the calculation of the absorbed location of the target MSW was made, the arm of this delta robot moved to absorb and then transfer the MSW to the bin. Results showed that the IMSWS prototype could sort the multi-object MSWs in the MSW stream. Both YOLOv3 and YOLOv4 reached high detection accuracy on the MSW image dataset. However, the improvement should be made in the actually moving MSW stream even though the YOLOv4 performed the acceptable detection accuracy. The gripping stability of the arm mainly dominated the performance of IMSWS, and this should be improved first.

Bioassay-guided isolation and characterisation of α-glucosidase inhibitors from Sanghuangporus baumii.

Bioassay-guided fractionation of the isopropanol extract of the medicinal mushroom Sanghuangporus baumii led to the isolation and characterisation of a new acorane-type sesquiterpenoid bauminene (1) and seven known compounds 2-8. The planar structure of 1 was elucidated on the basis of extensive spectroscopic analysis, including 1D, 2D NMR and HR-ESI-MS. The relative configuration of 1 was determined by a combination of ROESY experiment, density functional theory calculation of 13C NMR, and DP4+ probability analysis, while the absolute configuration of 1 was established by comparative electronic circular dichroism (ECD) spectra analysis. In the in vitro bioassay, compounds 1-8 exhibited potent to moderate α-glucosidase inhibitory activity with IC50 values ranging from 6.8 ± 0.68 to 221.4 ± 6.57 µM. The presences of these bioactive constituents in the sclerotia of S. baumii may be related to the use of the fungus as 'Sanghuang' for the adjuvant treatment of DM.

Significance of radiologic extranodal extension in locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis: a comprehensive nomogram.

OBJECTIVE: We aimed to assess the significance of rENE and creat a predictive tool (nomogram) for estimating Overall Survival (OS) in locoregionally advanced Nasopharyngeal Carcinoma (NPC) patients with Lymph Node Metastasis (LNM) based on their clinical characteristics and Radiologic Extranodal Extension (rENE). METHODS: Five hundred and sixty-nine NPC patients with LNM were randomly divided into training and validation groups. Significant factors were identified using univariate and multivariate analyses in the training cohort. Then, the nomogram based on the screening results was established to predict the Overall Survival (OS). Calibration curves and the Concordance index (C-index) gauged predictive accuracy and discrimination. Receiver Operating Characteristic (ROC) analysis assessed risk stratification, and clinical utility was measured using Decision Curve Analysis (DCA). The nomogram's performance was validated for discrimination and calibration in an independent validation cohort. RESULTS: A total of 360 (63.2%) patients were present with radiologic extranodal extension at initial diagnosis. Patients with rENE had significantly lower OS than other patients. Multivariate analysis identified the five factors, including rENE, for the nomogram model. The C-index was 0.75 (0.71-0.78) in the training cohort and 0.76 (0.69-0.83) in the validation cohort. Notably, the nomogram outperformed the 8th TNM staging system, as evident from the higher AUC values (0.77 vs. 0.60 for 2year and 0.75 vs. 0.65 for 3year) and well-calibrated calibration curves. Decision curve analysis indicated improved Net Benefit (NB) with the nomogram for predicting OS. The log-rank test confirmed significant survival distinctions between risk groups in both training and validation cohorts. CONCLUSIONS: We demonstrated the prognostic value of rENE in nasopharyngeal carcinoma and developed a nomogram based on rENE and other factors to provide individual prediction of OS for locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis. LEVEL OF EVIDENCE: III.

Comparison of mid-outcome among bare metal stent, atherectomy with or without drug-coated balloon angioplasty for femoropopliteal arterial occlusion.

This study evaluated the outcomes of a bare metal stent (BMS), DCB alone, atherectomy plus a drug-coated balloon (AT + DCB) and AT alone for the treatment of femoropopliteal artery occlusion. Four groups were included in this retrospective cohort study: 119 patients underwent the BMS procedure, 89 patients underwent DCB alone, 52 patients underwent AT + DCB, and 61 patients underwent AT alone. Patients were followed-up at 1, 6, 12 and 24 months after the procedure, the clinical outcomes and complications were assessed, and the primary outcomes were primary patency and restenosis. AT + DCB showed a lower bailout stent, and BMS displayed a higher retrograde puncture, flow-limiting dissection and postdilation (p < 0.05). For all procedures, the walking distance, ABI and pain score post-procedure were significantly improved compared with the pre-procedure values (p < 0.001). The restenosis rate was higher in BMS (21.0%) and AT alone (24.6%) than in DCB (10.1%) alone and AT + DCB (11.5%) (p = 0.04); there was no difference in amputation or clinically driven target lesion revascularization among procedures. The primary patency rates were 77.7%, 89.4%, 88.0% and 73.7% in the BMS, DCB alone, AT + DCB and AT alone groups at 24 months, respectively (p = 0.03), while the secondary patency and main adverse events (stroke, MI and death) were similar. Proximal concavity, proximal target vessel diameter ≥ 5 mm, runoff number ≥ 2 and DCB use were protective factors for primary patency. Our results suggested that AT + DCB and DCB alone were associated with higher primary patency, and DCB devices (combined with/without AT) should be the preferred choice for FP lesions.

Secondary metabolites from Penicillium sp. HS-11, a fungal endophyte of Huperzia serrata.

Three new sorbicillinoids sorbicatechols E-G (1-3), along with seven known compounds 4-10, were obtained from the ethanol extract of Penicillium sp. HS-11, a fungal endophyte of the medicinal plant Huperzia serrata. The structures of 1-3 were established by detailed interpretation of the spectroscopic data and their absolute configurations were established by comparative analyses of the ECD spectra. Sorbicatechol G (3) represented the first hybrid sorbicillinoid bearing a tetralone skeleton. In the in-vitro bioassay, trichodimerol (5) exhibited moderate inhibitory activity against the Escherichia coli ß-glucuronidase (EcGUS) with an IC50 value of 92.0 ± 9.4 µM.

Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

Microstructural changes of the white matter in systemic lupus erythematosus patients without neuropsychiatric symptoms: a multi-shell diffusion imaging study.

BACKGROUND: Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) provide more comprehensive and informative perspective on microstructural alterations of cerebral white matter (WM) than single-shell diffusion tensor imaging (DTI), especially in the detection of crossing fiber. However, studies on systemic lupus erythematosus patients without neuropsychiatric symptoms (non-NPSLE patients) using multi-shell diffusion imaging remain scarce. METHODS: Totally 49 non-NPSLE patients and 41 age-, sex-, and education-matched healthy controls underwent multi-shell diffusion magnetic resonance imaging. Totally 10 diffusion metrics based on DKI (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis and radial kurtosis) and NODDI (neurite density index, orientation dispersion index and volume fraction of the isotropic diffusion compartment) were evaluated. Tract-based spatial statistics (TBSS) and atlas-based region-of-interest (ROI) analyses were performed to determine group differences in brain WM microstructure. The associations of multi-shell diffusion metrics with clinical indicators were determined for further investigation. RESULTS: TBSS analysis revealed reduced FA, AD and RK and increased ODI in the WM of non-NPSLE patients (P < 0.05, family-wise error corrected), and ODI showed the best discriminative ability. Atlas-based ROI analysis found increased ODI values in anterior thalamic radiation (ATR), inferior frontal-occipital fasciculus (IFOF), forceps major (F_major), forceps minor (F_minor) and uncinate fasciculus (UF) in non-NPSLE patients, and the right ATR showed the best discriminative ability. ODI in the F_major was positively correlated to C3. CONCLUSION: This study suggested that DKI and NODDI metrics can complementarily detect WM abnormalities in non-NPSLE patients and revealed ODI as a more sensitive and specific biomarker than DKI, guiding further understanding of the pathophysiological mechanism of normal-appearing WM injury in SLE.

A machine learning approach for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma undergoing tomotherapy.

The purpose of this study was to establish an integrated predictive model that combines clinical features, DVH, radiomics, and dosiomics features to predict RIHT in patients receiving tomotherapy for nasopharyngeal carcinoma. Data from 219 patients with nasopharyngeal carcinoma were randomly divided into a training cohort (n = 175) and a test cohort (n = 44) in an 8:2 ratio. RIHT is defined as serum thyroid-stimulating hormone (TSH) greater than 5.6 µU/mL, with or without a decrease in free thyroxine (FT4). Clinical features, 27 DVH features, 107 radiomics features and 107 dosiomics features were extracted for each case and included in the model construction. The least absolute shrinkage and selection operator (LASSO) regression method was used to select the most relevant features. The eXtreme Gradient Boosting (XGBoost) was then employed to train separate models using the selected features from clinical, DVH, radiomics and dosiomics data. Finally, a combined model incorporating all features was developed. The models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. In the test cohort, the area under the receiver operating characteristic curve (AUC) for the clinical, DVH, radiomics, dosiomics and combined models were 0.798 (95% confidence interval [CI], 0.656-0.941), 0.673 (0.512-0.834), 0.714 (0.555-0.873), 0.698 (0.530-0.848) and 0.842 (0.724-0.960), respectively. The combined model exhibited higher AUC values compared to other models. The decision curve analysis demonstrated that the combined model had superior clinical utility within the threshold probability range of 1% to 79% when compared to the other models. This study has successfully developed a predictive model that combines multiple features. The performance of the combined model is superior to that of single-feature models, allowing for early prediction of RIHT in patients with nasopharyngeal carcinoma after tomotherapy.

Development of monoclonal antibodies targeting the conserved fragment of hexon protein to detect different serotypes of human adenovirus.

Human adenovirus (HAdV) infects the respiratory system, thus posing a threat to health. However, immunodiagnostic reagents for human adenovirus are limited. This study aimed to develop efficient diagnostic reagents based on monoclonal antibodies for diagnosing various human adenovirus infections. Evolutionary and homology analyses of various human adenoviral antigen genes revealed highly conserved antigenic fragments. The prokaryotic expression system was applied to recombinant penton, hexon, and IVa2 conserved fragments of adenovirus, which were injected into BALB/c mice to prepare human adenovirus-specific monoclonal antibodies. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Western blotting were used to determine the immune specificity of the monoclonal antibodies. Indirect ELISA showed that monoclonal antibodies 1F10, 8D3, 4A1, and 9B2 were specifically bound to HAdV-3 and HAdV-55 and revealed high sensitivity and low detection limits for various human adenoviruses. Western blotting showed that 1F10 and 8D3 specifically recognized various human adenovirus types, including HAdV-1, HAdV-2, HAdV-3, HAdV-4, HAdV-5, HAdV-7, HAdV-21, and HAdV-55, and 4A1 specifically recognized HAdV-1, HAdV-2, HAdV-3, HAdV-5, HAdV-7, HAdV-21, and HAdV-55. IFAs showed that 1F10, 8D3, and 4A1 exhibited highly selective localization to A549 cells infected with HAdV-3 and HAdV-55. Finally, two antibody pairs that could detect hexon antigens HAdV-3 and HAdV-55 at low concentrations were developed. The monoclonal antibodies developed in this study show potential for detecting human adenoviruses. IMPORTANCE: In this study, we selected the three most conserved antigenic fragments of human adenovirus to prepare a murine monoclonal antibody for the first time, and human adenovirus antigenic fragments with heretofore unheard of degrees of conservatism were isolated. The three monoclonal antibodies with the ability to recognize human respiratory adenovirus over a broad spectrum were screened by hybridoma and monoclonal antibody preparation. Human adenovirus infections are serious; however, therapeutic drugs and diagnostic reagents are scarce. Thus, to reduce the serious consequences of human viral infections and adenovirus pneumonitis, early diagnosis of infection is required. The present study provides three monoclonal antibodies capable of recognizing a wide range of human adenoviruses, thereby offering guidance for subsequent research and development.