Effects of dietary Chinese yam polysaccharide copper complex on growth performance, immunity, and antioxidant capacity of broilers.

Chinese yam polysaccharide (CYP) has received attention in recent years owing to its positive nutritional and medicinal characteristics. Copper is an essential trace metal in animals, which plays an important role in iron absorption and hemoglobin synthesis. However, no published study has evaluated Chinese yam polysaccharide copper complex (CYP-Cu) as a dietary additive in broilers. This study was conducted to investigate the effects of dietary CYP-Cu on growth performance, immunity, and oxidative resistance in broilers. A total of 360 1-day-old 817 broiler chickens were randomly divided into 4 groups, with 3 replicates of 30 birds each and were fed a basal diet with the addition of 0 (control group), 0.02, 0.10, and 0.50 g/kg CYP-Cu. The feeding trial lasted 48 days. On day 28 and day 48, 6 broilers in each group were slaughtered, respectively. Then the parameters of growth and carcass, serum biochemistry, immunity, and antioxidation, and the expression level of hepatic antioxidative genes were investigated. The results showed that compared with the control group, the supplementation of dietary CYP-Cu could improve the indexes of the growth, carcass, serum biochemistry, immunity and oxidation resistance in broilers, such as average daily gain (ADG), the slaughter percentage (SP), semi-evisceration weight percentage (SEWP), eviscerated carcass weight percentage (EWP), breast muscle percentage (BMP), leg muscle percentage (LMP), serum albumin (ALB), high density lipoprotein (HDL), insulin-like growth factor I (IGF-I), triiodothyronine (T3), thyroxine (T4), growth hormone (GH), insulin (INS), immunoglobulin M (IgM), immunoglobulin G (IgG), immunoglobulin A (IgA), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), complement 3 (C3), complement 4 (C4), total superoxide dismutase (T-SOD), total antioxidative capacity (T-AOC), glutathione peroxidase (GSH-Px), and glutathione s-transferase (GSH-ST); these parameters in the 0.10 g/kg CYP-Cu treated group were significantly increased (P < 0.05) in the total trial period, with the exceptions that feed conversion ratio (FCR) and serum low density lipoprotein (LDL), malondialdehyde (MDA) were decreased in the total trial period. In addition, the antioxidative gene mRNA expression of Nuclear factor E2-related factor 2 (Nrf 2), Superoxide dismutase 1 (SOD 1), Superoxide dismutase 2 (SOD 2), and Catalase (CAT) were upregulated in the liver (P < 0.05). These results indicated that the supplementation of dietary CYP-Cu improved the growth, immunity, and oxidation resistance of broilers, and the addition of 0.10 g/kg CYP-Cu in broiler diets is recommended, which suggests that CYP-Cu may be a promising green feed additive in the poultry industry.

Effects of receiving renal biopsy on the prognosis of chronic kidney disease patients with impaired renal function.

BACKGROUND: Impaired renal function was not a recognized indication for renal biopsy. The effects of receiving renal biopsy on the renal functional prognosis for chronic kidney disease (CKD) patients with impaired renal function need to be explored. METHODS: This study retrospectively enrolled 300 renal function impaired CKD patients in Renji Hospital from January 2015 to December 2017, 150 of them received percutaneous renal biopsy while the others did not. The endpoint was ≥ 50% estimated glomerular filtration rate (eGFR) decline from baseline or development of end-stage renal disease (ESRD). Kaplan-Meier analysis with log-rank test was performed to compare the renal survival probability between patients receiving renal biopsy or not. Univariate and multivariate analysis with Cox regression were conducted with predictors of poor renal outcomes in the study cohort. RESULTS: The median follow-up period was 37.6 months. During the follow-up period, the eGFR of the biopsy group increased from 52.2 ± 14.4 to 67.4 ± 37.8 ml/min/1.73 m², but decreased from 55.3 ± 17.1 to 29.8 ± 19.1 ml/min/1.73 m² in the non-biopsy group. Patients who received renal biopsy had significantly higher renal survival probability (P < 0.001). Cox regression analysis revealed that 24-hour urine protein excretion (24 h UPE) more than 1 g/d was an independent predictor for poor renal outcomes in the non-biopsy group but not in the renal biopsy group (HR = 1.719, P = 0.040). CONCLUSION: CKD patients with impaired renal function are recommended to receive renal biopsy to make pathological diagnoses, especially for those with the 24-hour urine protein excretion more than 1 g/d.

Frequent EGFR exon 20 insertion in the so-called peripheral-type squamous cell neoplasm of uncertain malignant potential: a variant of bronchiolar adenoma or under-recognised entity?

INTRODUCTION: Herein we describe a series of rare peripheral pulmonary neoplasms temporarily termed "peripheral type squamous cell neoplasm of uncertain malignant potential (PSCN-UMP)" and investigate their relationship to bronchiolar adenoma (BA) and squamous cell carcinoma (SCC). MATERIALS AND METHODS: The histologic and immunohistochemical features of 10 PSCN-UMPs and six BAs were compared. Whole exome sequencing (WES) and bioinformatics analysis were performed to further compare the genetic features of PSCN-UMPs, BAs, and NSCLCs. RESULTS: All PSCN-UMPs were peripherally located and histologically characterised by the lepidic, nested, and papillary proliferation of relatively bland squamous cells, accompanied by entrapped hyperplastic reactive pneumocytes. The basal squamous cells coexpressed TTF1 and squamous markers. Both cellular components exhibited bland morphology and a low proliferative activity. The six BAs met the morphologic and immunophenotypic features of proximal-type BA. Genetically, driver mutations, including frequent EGFR exon 20 insertions, were found in PSCN-UMPs, while the KRAS mutation, BRAF mutation, and ERC1::RET fusion were detected in BAs. PSCN-UMPs also shared some alterations with BAs in mutational signatures, while copy number variants (CNV) were enriched in MET and NKX2-1 in PSCN-UMP and MCL1, MECOM, SGK1, and PRKAR1A in BA. CONCLUSION: PSCN-UMPs exhibited the proliferation of bland squamous cells accompanied by entrapped pneumocytes and frequent EGFR exon 20 insertions, which showed distinct features from BAs and SCCs. Recognition of this specific entity will help to expand the morphologic and molecular spectrum of peripheral lung squamous neoplasms.

External counterpulsation stimulation combined with acupuncture for vascular endothelial function in patients with hypertension: A randomized pilot trial.

OBJECTIVE: Endothelial function may improve with enhanced external counterpulsation (EECP) or acupuncture. This study aimed to evaluate the feasibility of acupoint stimulation combined with EECP (acupoint-EECP) for endothelial cell function in patients with essential hypertension. METHODS: Thirty essential hypertensive patients were, randomly divided into two groups, with 15 patients in the acupoint-EECP group, and 15 patients in the control group, of which 3 cases were lost by week 6. Both groups were treated with continued medicine. The participants in the acupoint-EECP group received acupoint stimulation combined with EECP therapy, 45 min for each time, 5 times weekly for 6 weeks for a total of 22.5 hours. The selected acupoints are Zusanli (ST36), Fenglong (ST40) and Sanyinjiao (SP6). The curative effects of the two groups were compared. RESULTS: The acupoint-EECP group (n=15) showed significant improvement in endothelial function [nitric oxide (NO) ，endothelin-1 (ET-1) and carotid-femoral pulse wave velocity (cf-PWV), respectively] values compared to the control group (n=12). Multiple imputation (n = 20 imputations) was performed to account for potential bias due to missing data. In stratified analyses, SBP and DBP values decreased when the baseline SBP was ≥120 mmHg and DBP was ≥80 mmHg. CONCLUSIONS: These findings suggest the feasibility of acupoint-EECP in improving endothelial function and treating hypertension. (The Chinese clinical trial registration number is ChiCTR2100053795.).

Role of inflammation in neurological damage and regeneration following spinal cord injury and its therapeutic implications.

Spinal cord injury (SCI) is an incurable trauma that frequently results in partial or complete loss of motor and sensory function. Massive neurons are damaged after the initial mechanical insult. Secondary injuries, which are triggered by immunological and inflammatory responses, also result in neuronal loss and axon retraction. This results in defects in the neural circuit and a deficiency in the processing of information. Although inflammatory responses are necessary for spinal cord recovery, conflicting evidence of their contributions to specific biological processes have made it difficult to define the specific role of inflammation in SCI. This review summarizes our understanding of the complex role of inflammation in neural circuit events following SCI, such as cell death, axon regeneration and neural remodeling. We also review the drugs that regulate immune responses and inflammation in the treatment of SCI and discuss the roles of these drugs in the modulation of neural circuits. Finally, we provide evidence about the critical role of inflammation in facilitating spinal cord neural circuit regeneration in zebrafish, an animal model with robust regenerative capacity, to provide insights into the regeneration of the mammalian central nervous system.

Shewanella oneidensis MR-1 and oxalic acid mediated vanadium reduction and redistribution in vanadium-containing tailings.

The microbially- and chemically-mediated redox process is critical in controlling the fate of vanadium (V) in tailing environment. Although the microbial reduction of V has been widely studied, the coupled biotic reduction mediated by beneficiation reagents and the underlying mechanism remain unclear. Herein, the reduction and redistribution of V in V-containing tailings and Fe/Mn oxide aggregates mediated by Shewanella oneidensis MR-1 and oxalic acid were explored. The dissolution of Fe-(hydr)oxides by oxalic acid promoted the microbe-mediated V release from solid-phase. After 48-day of reaction, the dissolved V concentrations in the bio-oxalic acid treatment reached maximum values of 1.72 ± 0.36 mg L-1 and 0.42 ± 0.15 mg L-1 in the tailing system and the aggregate system, respectively, significantly higher than those in control (0.63 ± 0.14 mg L-1 and 0.08 ± 0.02 mg L-1). As the electron donor, oxalic acid enhanced the electron transfer process of S. oneidensis MR-1 for V(V) reduction. The mineralogical characterization of final products indicates that S. oneidensis MR-1 and oxalic acid promoted solid-state conversion from V2O5 to NaV6O15. Collectively, this study demonstrates that microbe-mediated V release and redistribution in solid-phase were promoted by oxalic acid, suggesting that the role of organic agents for the V biogeochemical cycle in natural systems deserves greater attention.

[Vertical Distribution and Source Tracking Analysis of Bacteria Composition and Nitrogen Metabolism Function of a Typical Urban Inland River].

Microorganisms play an important role in the urban river nitrogen cycle. Due to the three-dimensional fluidity of river water, it is necessary to clarify the vertical distribution of community composition and nitrogen metabolism functions of microorganisms and discover how hydrodynamic factors influence microorganism sources and community composition. Based on 16S rRNA high-throughput sequencing technology, the bacteria community composition and nitrogen metabolism function of water and sediment in the North Canal at Tongzhou District Beijing City were analyzed. The effect of environmental and hydrodynamic factors on community composition and sources were studied. The results showed that the α diversity of sediment was significantly higher than that of water. Proteobacteria was the most abundant phylum, which accounted for 54.72% and 32.36% in water and sediment, respectively. Functional prediction conducted using PICRUSt2 showed that the studied North Canal had an abundance of nitrogen metabolism ability, and 47 genes related to the nitrogen cycle were obtained. Water and sediment microorganisms had a similar distribution of nitrogen metabolism functions. The copy number of genes involved with denitrification, nitrogen assimilation, and dissimilation-reduction were high, whereas the abundance of genes related to biological nitrogen fixation and nitrification were relatively low. Source tracking analysis showed that bacteria in the water that originated from upstream, neighboring sides, and sediment were 60.05%, 37.93%, and 1.05%, respectively. The amounts of bacteria in sediment that migrated from upstream, neighboring sides, and water were 50.16%, 45.55%, and 1.55%, respectively. Environmental factors, hydrodynamic conditions, and their interactions explained water bacteria community composition for 44.22%, 3.21%, and 15.60%, respectively. For sediment bacteria, the degree of explanation was 13.05%, 1.56%, and 8.51%, respectively. This indicated that environmental factors and hydrodynamic factors controlled the community composition and nitrogen cycle functions together.

FAM69C functions as a kinase for eIF2α and promotes stress granule assembly.

Stress granules are dynamic cytoplasmic ribonucleoprotein granules that assemble in response to cellular stress. Aberrant formation of stress granules has been linked to neurodegenerative diseases. However, the molecular mechanisms underlying the initiation of stress granules remain elusive. Here we report that the brain-enriched protein kinase FAM69C promotes stress granule assembly through phosphorylation of eukaryotic translation initiation factor 2 (eIF2α). FAM69C physically interacts with eIF2α and functions as a stress-specific kinase for eIF2α, leading to stress-induced protein translation arrest and stress granule assembly. Primary microglia derived from Fam69c knockout mice exhibit aberrant stress granule assembly in response to oxidative stress and ATP. Defective stress granule assembly in microglia correlates with the formation of ASC specks and NLRP3 inflammasome activation, whereas induction of stress granule precludes inflammasome formation. Consistently, increased NLRP3 levels, caspase-1 cleavage and Il18 expression corroborate microglia-associated neuroinflammation in aged Fam69c knockout mice. Our study demonstrates that FAM69C is critical for stress granule assembly and suggests its role in the regulation of microglia function.

Functional dysconnectivity of anterior cingulate subregions in schizophrenia and psychotic and nonpsychotic bipolar disorder.

Aberrant resting-state functional connectivity (FC) of anterior cingulate cortex (ACC) has been implicated in the pathophysiology of schizophrenia and bipolar disorder (BP). This study investigated the subregional FC of ACC across schizophrenia and psychotic (PBP) and nonpsychotic BP (NPBP) and the relationship between brain functional alterations and clinical manifestations. A total of 174 first-episode medication-naive patients with schizophrenia (FES), 80 patients with PBP, 77 patients with NPBP and 173 demographically matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Brain-wide FC of ACC subregions was computed for each individual, and compared between the groups. General intelligence was evaluated using the short version of the Wechsler Adult Intelligence Scale. Relationships between FC and various clinical and cognitive variables were estimated using the skipped correlation. The FES, PBP and NPBP groups showed differing connectivity patterns in the left caudal, dorsal and perigenual ACC. Transdiagnostic dysconnectivity was found in the subregional ACC associated with cortical, limbic, striatal and cerebellar regions. Disorder-specific dysconnectivity in FES was identified between the left perigenual ACC and bilateral orbitofrontal cortex, and the left caudal ACC coupling with the default mode network (DMN) and visual processing region was correlated with psychotic symptoms. In the PBP group, FC between the left dorsal ACC and the right caudate was correlated with psychotic symptoms, and FC connected with the DMN was associated with affective symptoms. The current findings confirmed that subregional ACC dysconnectivity could be a key transdiagnostic feature and associated with differing clinical symptomology across schizophrenia and PBP.

SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics.

RATIONALE/OBJECTIVES: Genetic studies suggest SOX17 deficiency increases pulmonary arterial hypertension (PAH) risk. Based on pathological roles of estrogen and hypoxia inducible factor 2α (HIF-2α) signaling in PA endothelial cells (PAECs), we hypothesized that SOX17 is a target of estrogen signaling that promotes mitochondrial function and attenuates PAH development via HIF-2α inhibition. METHODS: We used metabolic (seahorse) and promoter lucifer assays in PAECs along with the chronic hypoxia murine model to test the hypothesis. MEASUREMENTS AND MAIN RESULTS: Sox17 expression was reduced in PAH tissues (rodent models and from patients). Chronic hypoxic PH was exacerbated by mice with conditional Tie2-Sox17 (Sox17EC-/-) deletion and attenuated by transgenic Tie2-Sox17 over-expression (Sox17Tg). Based on untargeted proteomics, metabolism was the top pathway altered by SOX17 deficiency in PAECs. Mechanistically, we found HIF-2α levels were increased in the lungs of Sox17EC-/- and reduced in those from Sox17Tg mice. Increased SOX17 promoted oxidative phosphorylation and mitochondrial function in PAECs, which were partly attenuated by HIF-2α overexpression. Rat lungs in males displayed higher Sox17 expression versus females, suggesting repression by estrogen signaling. Supporting 16alpha-hydroxyestrone (16αOHE, a pathologic estrogen metabolite)-mediated repression of SOX17 promoter activity, Sox17Tg mice attenuated 16αOHE-mediated exacerbations of chronic hypoxic PH. Finally, in adjusted analyses in patients with PAH, we report novel associations between a SOX17 risk variant, rs10103692, with reduced plasma citrate levels (n=1326). CONCLUSIONS: Cumulatively, SOX17 promotes mitochondrial bioenergetics and attenuates PAH, in part, via inhibition of HIF-2α. 16αOHE mediates PAH development via downregulation of SOX17, linking sexual dimorphism and SOX17 genetics in PAH. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Photo-Activated Circularly Polarized Luminescence Film Based on Aggregation-Induced Emission Copper(I) Cluster-Assembled Materials.

In this study, a pair of chiral copper(I) cluster-assembled materials (R/S-2) was prepared, exhibiting unique photo-response characteristics with a concentration-wavelength correlation property in DMSO solution. By the combination of R/S-2 with a polymethyl methacrylate (PMMA) matrix, the first photo-activated circularly polarized luminescence (CPL) film was developed, the CPL signal (glum = 9×10-3) of which could be induced by UV light irradiation. Moreover, the film exhibited a reversible photo-response and extremely good fatigue resistance. Mechanism study revealed that the photo-response properties of the R/S-2 solution and film are attributed to the aggregation-induced emission (AIE) characteristics of R/S-2 and a photo-induced deoxygenation process. This study enriches the types of luminescent cluster-assembled molecules and provides a new strategy for the construction of metal cluster-based stimuli-responsive composite materials.

Effects of Dietary Supplementation of Chinese Yam Polysaccharide on Carcass Composition, Meat Quality, and Antioxidant Capacity in Broilers.

The study aimed to evaluate the influences of the dietary supplementation of Chinese yam polysaccharide (CYP) on the carcass performance, antioxidant capacity, and meat quality of broilers. Three hundred and sixty healthy 1-day-old broilers with similar body weight (39 ± 1 g, gender balanced) were randomly divided into four groups (control, CYP1, CYP2, and CYP3 groups). In the control group, broilers were fed a basal diet with CYP, and the CYP1, CYP2, and CYP3 groups were fed diets supplemented with 250, 500, and 1000 mg/kg CYP, respectively. There were three replicates in each group, 30 birds in each replicate, and the feeding trial lasted for 48 days. Statistical analysis was performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA) by one-way analysis of variance. The results showed that compared with the control group, dietary supplementation with 500 mg/kg CYP can improve live weight, half-eviscerated carcass percentage, eviscerated carcass percentage, and thigh muscle percentage. Moreover, dietary supplementation with 500 mg/kg CYP can improve the contents of total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GPX), and glutathione s-transferase (GST) in serum (p < 0.05). Meanwhile, the mRNA expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), and catalase (CAT) in the liver; the mRNA expression levels of HO-1, NQO1, GPX1, and CAT in the breast muscle; and the mRNA expression levels of NQO1, SOD1, and CAT in the thigh muscle of broilers in the CYP2 group were significantly increased (p < 0.05). In addition, the yellowness and shear force of the thigh and breast muscles and the content of malondialdehyde (MDA) in the serum of broilers in the control group were higher than that in the CYP2 groups (p < 0.05). The results demonstrated that the CYP2 group had the best effect on improving meat quality. In conclusion, dietary supplementation with 500 mg/kg CYP can improve the meat quality of broilers by improving carcass quality, meat color, shear force, and antioxidant capacity.

Automated study on kinetics and biosensing of glow-type luminescence reaction via digital microfluidics-chemiluminescence.

Automated manipulation of discrete droplets by digital microfluidics (DMF) combined with chemiluminescence (CL) is promising to achieve automated and sensitive biosensing and bioanalysis. Herein, a DMF-CL device was built to automatically study CL kinetics and biosensing of a glow-type CL reaction. Copper-cysteine nanoparticles (Cu/CysNP) were synthesized as a new CL catalyst to extend the CL reaction of luminol-H2O2 to more than 10 min. The automated manipulation of droplets reduced reagent costs and manual errors, leading to real-time, automated, and reliable study of CL kinetics. The CL kinetics curve collected by the DMF-CL integration device is in accordance with that of a commercial CL analyser. The long-lasting luminescence ensured automated, sensitive, and reliable detection of H2O2 as a direct or indirect analyte of the cascade catalytic reaction. Moreover, an innovative asymmetrical splitting method is proposed to quickly and precisely generate daughter droplets to ensure uniformity of the droplets and good repeatability of the DMF-CL measurements. Therefore, the DMF-CL analysis holds great potential for achieving online and automatic analysis and biosensing.

Up-regulation of HCN2 channels in a thalamocortical circuit mediates allodynia in mice.

Chronic pain is a significant problem that afflicts individuals and society, and for which the current clinical treatment is inadequate. In addition, the neural circuit and molecular mechanisms subserving chronic pain remain largely uncharacterized. Herein we identified enhanced activity of a glutamatergic neuronal circuit that encompasses projections from the ventral posterolateral nucleus (VPLGlu) to the glutamatergic neurons of the hindlimb primary somatosensory cortex (S1HLGlu), driving allodynia in mouse models of chronic pain. Optogenetic inhibition of this VPLGlu→S1HLGlu circuit reversed allodynia, whereas the enhancement of its activity provoked hyperalgesia in control mice. In addition, we found that the expression and function of the HCN2 (hyperpolarization-activated cyclic nucleotide-gated channel 2) were increased in VPLGlu neurons under conditions of chronic pain. Using in vivo calcium imaging, we demonstrated that downregulation of HCN2 channels in the VPLGlu neurons abrogated the rise in S1HLGlu neuronal activity while alleviating allodynia in mice with chronic pain. With these data, we propose that dysfunction in HCN2 channels in the VPLGlu→S1HLGlu thalamocortical circuit and their upregulation occupy essential roles in the development of chronic pain.

High nitrogen inhibits biomass and saponins accumulation in a medicinal plant Panax notoginseng.

Nitrogen (N) is an important macronutrient and is comprehensively involved in the synthesis of secondary metabolites. However, the interaction between N supply and crop yield and the accumulation of effective constituents in an N-sensitive medicinal plant Panax notoginseng (Burkill) F. H. Chen is not completely known. Morphological traits, N use and allocation, photosynthetic capacity and saponins accumulation were evaluated in two- and three-year-old P. notoginseng grown under different N regimes. The number and length of fibrous root, total root length and root volume were reduced with the increase of N supply. The accumulation of leaf and stem biomass (above-ground) were enhanced with increasing N supply, and LN-grown plants had the lowest root biomass. Above-ground biomass was closely correlated with N content, and the relationship between root biomass and N content was negatives in P. notoginseng (r = -0.92). N use efficiency-related parameters, NUE (N use efficiency, etc.), NC (N content in carboxylation system component) and P n (the net photosynthetic rate) were reduced in HN-grown P. notoginseng. SLN (specific leaf N), Chl (chlorophyll), NL (N content in light capture component) increased with an increase in N application. Interestingly, root biomass was positively correlated with NUE, yield and P n. Above-ground biomass was close negatively correlated with photosynthetic N use efficiency (PNUE). Saponins content was positively correlated with NUE and P n. Additionally, HN improved the root yield of per plant compared with LN, but reduced the accumulation of saponins, and the lowest yield of saponins per unit area (35.71 kg·hm-2) was recorded in HN-grown plants. HN-grown medicinal plants could inhibit the accumulation of root biomass by reducing N use and photosynthetic capacity, and HN-induced decrease in the accumulation of saponins (C-containing metabolites) might be closely related to the decline in N efficiency and photosynthetic capacity. Overall, N excess reduces the yield of root and C-containing secondary metabolites (active ingredient) in N-sensitive medicinal species such as P. notoginseng.

Multiclassifier Radiomics Analysis of Ultrasound for Prediction of Extrathyroidal Extension in Papillary Thyroid Carcinoma in Children.

Objective: To explore extrathyroidal extension (ETE) in children and adolescents with papillary thyroid carcinoma using a multiclassifier ultrasound radiomic model. Methods: In this study, data from 164 pediatric patients with papillary thyroid cancer (PTC) were retrospectively analyzed and patients were randomly divided into a training cohort (115) and a validation cohort (49) in a 7:3 ratio. To extract radiomics features from ultrasound images of the thyroid, areas of interest (ROIs) were delineated layer by layer along the edge of the tumor contour. The feature dimension was then reduced using the correlation coefficient screening method, and 16 features with a nonzero coefficient were chosen using Lasso. Then, in the training cohort, four supervised machine learning radiomics models (k-nearest neighbor, random forest, support vector machine [SVM], and LightGBM) were developed. ROC and decision-making curves were utilized to compare model performance, which was validated using validation cohorts. In addition, the SHapley Additive exPlanations (SHAP) framework was applied to explain the optimal model. Results: In the training cohort, the average area under the curve (AUC) was 0.880 (0.835-0.927), 0.873 (0.829-0.916), 0.999 (0.999-1.000), and 0.926 (0.892-0.926) for the SVM, KNN, random forest, and LightGBM, respectively. In the validation cohort, the AUC for the SVM was 0.784 (0.680-0.889), for the KNN, it was 0.720 (0.615-0.825), for the random forest, it was 0.728 (0.622-0.834), and for the LightGBM, it was 0.832 (0.742-0.921). Generally, the LightGBM model performed well in both the training and validation cohorts. From the SHAP results, original_shape_MinorAxisLength,original_shape_Maximum2DDiameterColumn, and wavelet-HHH_glszm_SmallAreaLowGrayLevelEmphasis have the most significant effect on the model. Conclusions: Our combined model based on machine learning and ultrasonic radiomics demonstrate the excellent predictive ability for extrathyroidal extension (ETE) in pediatric PTC.

Mortality Risk of Patients Treated in Dialysis Facilities with Payment Reductions under ESRD Quality Incentive Program.

BACKGROUND: The Centers for Medicare & Medicaid Services End-Stage Renal Disease Quality Incentive Program (ESRD QIP) measures quality of care delivered by dialysis facilities and imposes Medicare payment reductions for quality lapses. We assessed the association between payment reductions and patient mortality, a quality indicator not included in the ESRD QIP measure set. METHODS: Association between mortality and ESRD QIP facility payment reduction based on the year of performance was expressed as the unadjusted rate and patient case-mix-adjusted hazard ratio. We also measured association between mortality and 1-year changes in payment reductions. Retrospective patient cohorts were defined by their treating dialysis facility on the first day of each year (2010-2018). RESULTS: Facility performance resulted in payment reductions for 5%-42% of dialysis facilities over the 9 study years. Patients experienced progressively higher mortality at each payment reduction level. Across all years, unadjusted mortality was 17.3, 18.1, 18.9, 20.3, and 23.9 deaths per 100 patient-years for patients in facilities that received 0%, 0.5%, 1%, 1.5%, and 2% payment reductions, respectively. The adjusted hazard ratio showed a similar stepwise pattern by the level of payment reduction: 1.0 (reference), 1.08 (95% confidence interval [CI], 1.07 to 1.09), 1.15 (95% CI, 1.13 to 1.16), 1.19 (95% CI, 1.16 to 1.21), and 1.34 (95% CI, 1.29 to 1.39). Strength of the association increased from 2010 to 2016. Patients treated in facilities that improved over 1 year generally experienced lower mortality; patients in facilities that performed worse on ESRD QIP measures generally experienced higher mortality. CONCLUSIONS: Patient mortality was associated with ESRD QIP facility payment reductions in dose-response and temporal patterns.