Dual Nonradical Catalytic Pathways Mediated by Nanodiamond-Derived sp2/sp3 Hybrids for Sustainable Peracetic Acid Activation and Water Decontamination.

Peracetic acid (PAA) oxidation catalyzed by metal-free carbons is promising for advanced water decontamination. Nevertheless, developing reaction-oriented and high-performance carbocatalysts has been limited by the ambiguous understanding of the intrinsic relationship between carbon chemical/molecular structure and PAA transformation behavior. Herein, we comprehensively investigated the PAA activation using a family of well-defined sp2/sp3 carbon hybrids from annealed nanodiamonds (ANDs). The activity of ANDs displays a volcano-type trend, with respect to the sp2/sp3 ratio. Intriguingly, sp3-C-enriched AND exhibits the best catalytic activity for PAA activation and phenolic oxidation, which is different from persulfate chemistry in which the sp2 network normally outperforms sp3 hybridization. At the electron-rich sp2-C site, PAA undergoes a reduction reaction to generate a reactive complex (AND-PAA*) and induces an electron-transfer oxidation pathway. At the sp3-C site adjacent to C═O, PAA is oxidized to surface-confined OH* and O* successively, which ultimately evolves into singlet oxygen (1O2) as the primary reactive species. Benefiting from the dual nonradical regimes on sp2/sp3 hybrids, AND mediates a sustainable redox recycle with PAA to continuously generate reactive species to attack water contaminants, meanwhile maintaining structural/chemical integrity and exceptional reusability in cyclic runs.

An observational study of the pH value during the healing process of diabetic foot ulcer.

OBJECTIVE: In this study, we evaluated the pH (potential of hydrogen) value of diabetic foot ulcers and explored the relationship between the pH value and infection, sinus formation, stasis dermatitis, and the process of healing. METHODS: From October 2022 to June 2023, 99 patients with 106 diabetic foot ulcers were selected. Diabetic foot ulcers were treated in a standardized manner by a professional team. The pH value, area, PUSH (Pressure Ulcer Scale for Healing) score, and the degree of infection of the wounds were compared before and after the treatment. RESULTS: The baseline wound pH value in 76.4% of the patients was in the alkaline range and was closely related to the degree of infection (P < 0.05). As the ulcers healed, the pH decreased. For moderately and severely infected diabetic foot ulcers, each unit decrease in pH was associated with a decrease in the PUSH score of approximately 4.6 points (P < 0.05). The pH values of wounds with surrounding ecchymosis dermatitis were significantly higher than those of wounds without ecchymosis dermatitis (P < 0.05). The pH value of the wound with a sinus tract was higher. After treatment, there was no significant difference in pH value between the patients with and without sinus tracts (P < 0.05). CONCLUSIONS: The measurement of pH value is efficient and simple, and the patient suffers no discomfort in the process. The change in pH helps predict the healing process of diabetic foot ulcers and quickly identify whether there are key factors such as infection and ischemia in the wound. It is suggested that dynamic pH monitoring be included in the whole course evaluation and intervention strategy development of diabetic foot.

Sulfur enhances iron plaque formation and stress resistance to reduce the transfer of Cd and As in the soil-rice system.

Sulfur plays an essential role in agricultural production, but few studies have been reported on how sulfur simultaneously impacts the transformation of cadmium (Cd) and arsenic (As) in the soil-rice system. This research selected two soils co-contaminated with both Cd and As, varying in acidity and alkalinity levels, to study the impacts of elemental sulfur (S) and calcium sulfate (CaSO4) on the migration and accumulation of Cd and As by rice. Results indicated that two types of sulfur had a substantial (P < 0.05) impact on decreasing the contents of Cd (28.3-50.4 %) and As (20.1-38.6 %) in brown rice in acidic and alkaline soils. They also increased rice biomass (29.3-112.8 %) and reduced Cd transport coefficient (27.2-45.6 %) significantly (P < 0.05). Notably, sulfur augmented the generation of iron plaque on rice root surfaces, which increased the fixation of Cd (17.6-61.0 %) and As (14.0-45.9 %). SEM-EDS results also indicated that the rice root surface exhibited significant enrichment of Fe, Cd, and As. The mechanism of simultaneous Cd and As immobilization by sulfur application was mainly ascribed to the contribution of iron plaque. Additionally, sulfur reduced the contents of Cd and As in soil porewater and promoted the transformation of As(III) to As(V) to reduce the toxicity of As. The K-edge XAFS of As in iron plaque also confirmed that sulfur application significantly promoted As(III) oxidation. Sulfur also promoted the activities of antioxidant enzymes and the contents of NPT, GSH, and PCs in rice plants. In general, this study establishes a foundation for sulfur to lower As and Cd bioavailability in paddy soils, enhance iron plaque and rice resistance, and reduce heavy metal accumulation.

Full-face ALA-PDT for facial actinic keratosis: Two case reports.

We reported two cases of full-face 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) for facial multiple actinic keratosis (AK). After the full-face ALA-PDT, we observed that the AK lesions on the faces of the patients were completely cleared and facial rejuvenation was achieved. In our follow-up, one patient was free of recurrence for over 13 months and the other one for over 28 months. The experience of these two cases may indicate that full-face ALA-PDT has an excellent therapeutic effect while potentially preventing the recurrence of AK.

Sclerosing Angiomatoid Nodular Transformation of the Spleen: Radiological Findings and Radiological-pathological Correlation

Introduction: The objective of this study was to describe the CT and MRI features of sclerosing angiomatoid nodular transformation (SANT) of the spleen with pathologic correlation. Materials and Methods: Ten patients with surgically resected and pathologically confirmed SANTs were included. Clinical history was reviewed, and gross pathologic, histologic, and immunohistochemical findings were recorded. CT and MRI examinations were evaluated by two radiologists. Results: Patients included seven men and three women, with a mean age of 42.9±16.7 years. Pathologic features of SANTs involved multiple angiomatous nodules in a radiating pattern with a central stellate fibrous scar and evidence of hemosiderin deposition. 9 cases showed a lobulated demarcated margin, 8 cases a slight hypoattenuating, 1 isoattenuating, and 1 case with two lesions demonstrated a slight hyperattenuating margin, respectively. Multiple scattered punctate calcifications were involved in 2 cases. 5 cases manifested hypointensity on in-phase imaging, 1 iso-intensity, and 4 iso-hypointensity on out-of-phase imaging. Progressive and centripetal enhancement were exhibited in 10 cases, spoke-wheel pattern in 3 cases, and nodular enhancement in 4 cases, respectively. The central fibrous scar was identified in 8 cases during delayed enhancement. Conclusion: Characteristics of SANTs on CT/MRI reflected the underlying pathology. Hypointensity on DWI and T2WI, and change of signal on T1 chemicalshift imaging were found to be due to hemosiderin deposition and fibrous tissue. Typical feature was a solitary, round, lobulated mass with a fibrous scar. Progressive and centripetal enhancement, spoke-wheel pattern, nodular enhancement, and delayed enhancement of central fibrous scar were observed.

Insights into the epidemiology, risk factors, and clinical outcomes of carbapenem-resistant Acinetobacter baumannii infections in critically ill children.

Background and aims: Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a leading cause of nosocomial infections with an increasing impact on critically ill patients, yet there is limited data on contributing factors. This study was aim to evaluate the prevalence and risk factors, and clinical outcomes of CRAB infections among critically ill children in a tertiary university teaching hospital in China. Methods: From January 2016 to December 2021, all children diagnosed with nosocomial Acinetobacter baumannii (A. baumannii) infections in the pediatric intensive care unit (PICU) were identified through the computerized microbiology laboratory databases. Among them, children suffering from CRAB infection were designated as a case group, while children with carbapenem susceptible A. baumannii (CSAB) infection were assigned to a control group. This retrospective case-control study was based on two groups of patients to determine potential clinical factors contributing to CRAB infection and death among critically ill children via univariate and multivariate analyses. Results: During the 6-year study period, a total of 372 episodes of nosocomial A. baumannii infection in the PICU were eligible and included in the study. These isolates displayed moderate or high rates of resistance to all tested antimicrobials except colistin. The overall prevalence of CRAB and MDRAB (multidrug-resistant A. baumannii) was 78.0% and 80.9%, respectively. Several risk factors found to significantly increase CRAB infection included receiving invasive operation (OR = 9.412, p = 0.001), gastric intubation (OR = 2.478, p = 0.026), prior carbapenems exposure (OR = 2.543, p = 0.003), severe pneumonia (OR = 3.235, p = 0.001), and hemoglobin <110g/L (OR = 3.049, p = 0.005). Of 372 patients with CRAB infection, the mortality rate was 30.9% (115/372) and mortality did not differ between children with CRAB and CSAB infections. Septic shock (OR = 2.992, p = 0.001), AST > 46U/L (OR = 2.015, p = 0.005), bone marrow aspiration (OR = 2.704, p = 0.008), lymphocyte <20 % (OR = 1.992, p = 0.006) and age (OR = 1.094, p = 0.002) were independent risk factors for the death of A. baumanni infection. Conclusions: This study highlights considerable incidence rate and remarkable mortality of children with A. baumanni (especially CRAB) infections, and identifies age-specific risk factors for CRAB infection and mortality in critically ill children. These risk factors should be taken into account in pediatric hospitals in order to establish early intervention and rational treatment to improve clinical outcomes.

Renewable and efficient removal of arsenic from contaminated water by modified biochars derived from As-enriched plant.

There were limited researches on the scientific disposal of As-enriched plants, and how to reduce the available As content in the processed products and improve the utilization value were the key. In this study, the effect and mechanism of biochar produced by the As-enriched Pteris vittate before and after modification on the removal of As(III) in water were studied. The results indicated that the available As contents of Fe-BC300 and Fe-BC500 were reduced by 78.7 % and 91.9 % compared to original biochars, respectively. Modified biochars not only had a large adsorption capacity for As(III) (50.3 and 39.7 mg/g), but also can efficiently oxidize As(III) to As(V). The removal rate of As(III) by modified biochar was still higher than 50% after 3 cycles. The increase of the point of zero charge and the introduction of Fe were the main reasons for its efficient adsorption and oxidation of As(III).

A 15-year follow-up report of an elderly diabetic foot with multiple recurrences leading to toe amputation and thoughts on the model of care for diabetic foot ulcer.

Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Elderly diabetic patients are a high prevalence of diabetic foot ulcers, and their high recurrence, disability, and mortality rates impose a heavy economic burden on families and society. This paper reports a case of an elderly patient with a diabetic foot ulcer who was admitted in April 2007 and discharged after recovery from comprehensive diabetic foot treatment. Due to intermittent foot care and lack of home care, the patient's foot ulcers recurred after repeated healing during home rehabilitation, eventually resulting in the amputation of the right bunion. After the patient was discharged from the hospital with an amputated toe, the whole-process seamless management model of "hospital - community - family" was implemented. The hospital provides specialized foot support and guidance, and the community is responsible for daily disease management and referrals. The family is responsible for the implementation of home rehabilitation programs, and family caregivers need to identify and provide feedback on foot abnormalities promptly. As of May 2022, the patient had not experienced ulcer recurrence. This paper reports the whole process of "ulcer development → ulcer healing → ulcer recurrence healing → toe amputation → continuous care management" experienced by the patient in 15 years, aiming to reflect on the significance of the whole-process seamless foot care management model of "hospital-community-family" for diabetic foot ulcer rehabilitation through the case.

CD38 as a pan-hematologic target for chimeric antigen receptor T cells.

Many hematologic malignancies are not curable with chemotherapy and require novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy is 1 such approach that involves the transfer of T cells engineered to express CARs for a specific cell-surface antigen. CD38 is a validated tumor antigen in multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL) and is also overexpressed in acute myeloid leukemia (AML). Here, we developed human CD38-redirected T cells (CART-38) as a unified approach to treat 3 different hematologic malignancies that occur across the pediatric-to-adult age spectrum. Importantly, CD38 expression on activated T cells did not impair CART-38 cells expansion or in vitro function. In xenografted mice, CART-38 mediated the rejection of AML, T-ALL, and MM cell lines and primary samples and prolonged survival. In a xenograft model of normal human hematopoiesis, CART-38 resulted in the expected reduction of hematopoietic progenitors, which warrants caution and careful monitoring of this potential toxicity when translating this new immunotherapy into the clinic. Deploying CART-38 against multiple CD38-expressing malignancies is significant because it expands the potential for this novel therapy to affect diverse patient populations.

Prostate Ultrasound Image Segmentation Based on DSU-Net.

In recent years, the incidence of prostate cancer in the male population has been increasing year by year. Transrectal ultrasound (TRUS) is an important means of prostate cancer diagnosis. The accurate segmentation of the prostate in TRUS images can assist doctors in needle biopsy and surgery and is also the basis for the accurate identification of prostate cancer. Due to the asymmetric shape and blurred boundary line of the prostate in TRUS images, it is difficult to obtain accurate segmentation results with existing segmentation methods. Therefore, a prostate segmentation method called DSU-Net is proposed in this paper. This proposed method replaces the basic convolution in the U-Net model with the improved convolution combining shear transformation and deformable convolution, making the network more sensitive to border features and more suitable for prostate segmentation tasks. Experiments show that DSU-Net has higher accuracy than other existing traditional segmentation methods.

Generation of FeIV =O and its Contribution to Fenton-Like Reactions on a Single-Atom Iron-N-C Catalyst.

Generating FeIV =O on single-atom catalysts by Fenton-like reaction has been established for water treatment; however, the FeIV =O generation pathway and oxidation behavior remain obscure. Employing an Fe-N-C catalyst with a typical Fe-N4 moiety to activate peroxymonosulfate (PMS), we demonstrate that generating FeIV =O is mediated by an Fe-N-C-PMS* complex-a well-recognized nonradical species for induction of electron-transfer oxidation-and we determined that adjacent Fe sites with a specific Fe1 -Fe1 distance are required. After the Fe atoms with an Fe1 -Fe1 distance <4 Šare PMS-saturated, Fe-N-C-PMS* formed on Fe sites with an Fe1 -Fe1 distance of 4-5 Šcan coordinate with the adjacent FeII -N4 , forming an inter-complex with enhanced charge transfer to produce FeIV =O. FeIV =O enables the Fenton-like system to efficiently oxidize various pollutants in a substrate-specific, pH-tolerant, and sustainable manner, where its prominent contribution manifests for pollutants with higher one-electron oxidation potential.

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.

We conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)-negative complete response/stringent complete response. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T-cell reexpansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T-cell therapy in early lines of MM treatment. SIGNIFICANCE: CAR T cells in early lines of MM therapy could be safer and more effective than in the advanced setting, where prior studies have focused. We evaluated the safety, pharmacokinetics, and efficacy of CAR T cells in patients with low disease burden, responding to current therapy, combined with standard maintenance therapy. This article is highlighted in the In This Issue feature, p. 101.

Insights into the mechanism of carbocatalysis for peracetic acid activation: Kinetic discernment and active site identification.

Peracetic-acid-based advanced oxidation processes (PAA-AOPs) on metal-free catalysts have emerged as charming strategies for water contaminant removal. However, the involved reactive species and their corresponding active sites are ambiguous. Herein, using carbon nanotube (CNT) as a model carbocatalyst, we demonstrated that, under neutral conditions, the CNT-PAA* complex was the dominant reactive species to oxidize phenolic compounds via electron-transfer process (ETP), whereas the surface-bound hydroxyl radicals (·OHsurface) played a minor role on the basis of quenching and electrochemical tests as well as Raman spectroscopy. More importantly, the experimental and density functional theory (DFT) calculation results collaboratively proved that the active site for ETP was the sp2-hybridized carbon on the CNT bulk, while that for radical generation was the edge-located hydroxyl group (C-OH), which lowered the energy barrier for cleaving the O-O bond in CNT-PAA* complex. We further discerned the oxidation kinetic constants (koxid) of different pollutants from the apparent kinetic constants in CNT/PAA system. The significant negative linear correlation between lnkoxid and half-wave potential of phenolic compounds suggests that the pollutants with a lower one-electron oxidation potential (i.e., stronger electron-donating ability) are more easily oxidized. Overall, this study scrutinizes the hybrid radical and non-radical mechanism and the corresponding active sites of the CNT/PAA system, providing insights into the application of PAA-AOPs and the development of ETP in the remediation of emerging organic pollutants.

Electro-Induced Carbon Nanotube Discrete Electrodes for Sustainable Persulfate Activation.

In electrochemical advanced oxidation processes (EAOPs), the rate-limiting step is the mass transfer of pollutants to the electrodes due to the limited active surface areas. To this end, we established a three-dimensional (3D) EAOP system by coupling conventional graphite electrodes with dispersed carbon nanotubes (CNTs). The electrodes (particularly the anode) induced electric field spontaneously polarized CNTs into dispersed reactive particle electrodes (CNT-PEs) in the solution, which remarkably promoted electrochemical activation of peroxydisulfate (PDS) to generate surface CNT-PDS* complexes and surface-bound radicals (SBRs). Based on the excited potential (ECNT-PEs) at different positions in the 3D electric field, CNT-PEs were activated into three states. (i) ECNT-PEs < Eorganic, CNT-PEs are chemically inert toward DCP oxidation; (ii) Eorganic < ECNT-PEs < Ewater, CNT-PEs will oxidize DCP via an electron-transfer process (ETP); (iii) ECNT-PEs > Ewater, both CNT-PDS* complexes and the anode will oxidize water to produce SBRs. Thus, DCP could be oxidized by CNT-PDS* complexes via ETP to form polychlorophenols on the CNT surface, causing rapid deactivation of the micro-electrodes. In contrast, SBRs attack DCP directly into chloride ions and hydroxylated products, maintaining the surface cleanliness and activity of CNT-PEs for long-term operations.

Application value of a deep learning method based on a 3D V-Net convolutional neural network in the recognition and segmentation of the auditory ossicles.

Objective: To explore the feasibility of a deep learning three-dimensional (3D) V-Net convolutional neural network to construct high-resolution computed tomography (HRCT)-based auditory ossicle structure recognition and segmentation models. Methods: The temporal bone HRCT images of 158 patients were collected retrospectively, and the malleus, incus, and stapes were manually segmented. The 3D V-Net and U-Net convolutional neural networks were selected as the deep learning methods for segmenting the auditory ossicles. The temporal bone images were randomized into a training set (126 cases), a test set (16 cases), and a validation set (16 cases). Taking the results of manual segmentation as a control, the segmentation results of each model were compared. Results: The Dice similarity coefficients (DSCs) of the malleus, incus, and stapes, which were automatically segmented with a 3D V-Net convolutional neural network and manually segmented from the HRCT images, were 0.920 ± 0.014, 0.925 ± 0.014, and 0.835 ± 0.035, respectively. The average surface distance (ASD) was 0.257 ± 0.054, 0.236 ± 0.047, and 0.258 ± 0.077, respectively. The Hausdorff distance (HD) 95 was 1.016 ± 0.080, 1.000 ± 0.000, and 1.027 ± 0.102, respectively. The DSCs of the malleus, incus, and stapes, which were automatically segmented using the 3D U-Net convolutional neural network and manually segmented from the HRCT images, were 0.876 ± 0.025, 0.889 ± 0.023, and 0.758 ± 0.044, respectively. The ASD was 0.439 ± 0.208, 0.361 ± 0.077, and 0.433 ± 0.108, respectively. The HD 95 was 1.361 ± 0.872, 1.174 ± 0.350, and 1.455 ± 0.618, respectively. As these results demonstrated, there was a statistically significant difference between the two groups (P < 0.001). Conclusion: The 3D V-Net convolutional neural network yielded automatic recognition and segmentation of the auditory ossicles and produced similar accuracy to manual segmentation results.

Clinical evaluation of deep learning-based clinical target volume three-channel auto-segmentation algorithm for adaptive radiotherapy in cervical cancer.

OBJECTIVES: Accurate contouring of the clinical target volume (CTV) is a key element of radiotherapy in cervical cancer. We validated a novel deep learning (DL)-based auto-segmentation algorithm for CTVs in cervical cancer called the three-channel adaptive auto-segmentation network (TCAS). METHODS: A total of 107 cases were collected and contoured by senior radiation oncologists (ROs). Each case consisted of the following: (1) contrast-enhanced CT scan for positioning, (2) the related CTV, (3) multiple plain CT scans during treatment and (4) the related CTV. After registration between (1) and (3) for the same patient, the aligned image and CTV were generated. Method 1 is rigid registration, method 2 is deformable registration, and the aligned CTV is seen as the result. Method 3 is rigid registration and TCAS, method 4 is deformable registration and TCAS, and the result is generated by a DL-based method. RESULTS: From the 107 cases, 15 pairs were selected as the test set. The dice similarity coefficient (DSC) of method 1 was 0.8155 ± 0.0368; the DSC of method 2 was 0.8277 ± 0.0315; the DSCs of method 3 and 4 were 0.8914 ± 0.0294 and 0.8921 ± 0.0231, respectively. The mean surface distance and Hausdorff distance of methods 3 and 4 were markedly better than those of method 1 and 2. CONCLUSIONS: The TCAS achieved comparable accuracy to the manual delineation performed by senior ROs and was significantly better than direct registration.

Fortilin interacts with TGF-ß1 and prevents TGF-ß receptor activation.

Fortilin is a 172-amino acid multifunctional protein present in both intra- and extracellular spaces. Although fortilin binds and regulates various cellular proteins, the biological role of extracellular fortilin remains unknown. Here we report that fortilin specifically interacts with TGF-ß1 and prevents it from activating the TGF-ß1 signaling pathway. In a standard immunoprecipitation-western blot assay, fortilin co-immunoprecipitates TGF-ß1 and its isoforms. The modified ELISA assay shows that TGF-ß1 remains complexed with fortilin in human serum. Both bio-layer interferometry and surface plasmon resonance (SPR) reveal that fortilin directly bind TGF-ß1. The SPR analysis also reveals that fortilin and the TGF-ß receptor II (TGFßRII) compete for TGF-ß1. Both luciferase and secreted alkaline phosphatase reporter assays show that fortilin prevents TGF-ß1 from activating Smad3 binding to Smad-binding element. Fortilin inhibits the phosphorylation of Smad3 in both quantitative western blot assays and ELISA. Finally, fortilin inhibits TGFß-1-induced differentiation of C3H10T1/2 mesenchymal progenitor cells to smooth muscle cells. A computer-assisted virtual docking reveals that fortilin occupies the pocket of TGF-ß1 that is normally occupied by TGFßRII and that TGF-ß1 can bind either fortilin or TGFßRII at any given time. These data support the role of extracellular fortilin as a negative regulator of the TGF-ß1 signaling pathway.

Performance investigation of electrochemical assisted HClO/Fe2+ process for the treatment of landfill leachate.

The feasibility of removal of chemical oxygen demand (COD) and ammonia nitrogen (NH4+-N) from landfill leachate by an electrochemical assisted HClO/Fe2+ process is demonstrated for the first time. The performance of active chlorine generation at the anode was evaluated in Na2SO4/NaCl media, and a higher amount of active chlorine was produced at greater chloride concentration and higher current density. The probe experiments confirmed the coexistence of hydroxyl radical (•OH) and Fe(IV)-oxo complex (FeIVO2+) in the HClO/Fe2+ system. The influence of initial pH, Fe2+ concentration, and applied current density on COD and NH4+-N abatement was elaborately investigated. The optimum pH was found to be 3.0, and the proper increase in Fe2+ dosage and current density resulted in higher COD removal due to the accelerated accumulation of •OH and FeIVO2+ in the bulk liquid phase, whereas, the NH4+-N oxidation was significantly affected by the applied current density because of the effective active chlorine generation at higher current but was nearly independent of Fe2+ concentration. The reaction mechanism of electrochemical assisted HClO/Fe2+ treatment of landfill leachate was finally proposed. The powerful •OH and FeIVO2+, in concomitance with active chlorine and M(•OH), were responsible for COD abatement, and active chlorine played a key role in NH4+-N oxidation. The proposed electrochemical assisted HClO/Fe2+ process is a promising alternative for the treatment of refractory landfill leachate.

Deep learning-based auto-segmentation of clinical target volumes for radiotherapy treatment of cervical cancer.

OBJECTIVES: Because radiotherapy is indispensible for treating cervical cancer, it is critical to accurately and efficiently delineate the radiation targets. We evaluated a deep learning (DL)-based auto-segmentation algorithm for automatic contouring of clinical target volumes (CTVs) in cervical cancers. METHODS: Computed tomography (CT) datasets from 535 cervical cancers treated with definitive or postoperative radiotherapy were collected. A DL tool based on VB-Net was developed to delineate CTVs of the pelvic lymph drainage area (dCTV1) and parametrial area (dCTV2) in the definitive radiotherapy group. The training/validation/test number is 157/20/23. CTV of the pelvic lymph drainage area (pCTV1) was delineated in the postoperative radiotherapy group. The training/validation/test number is 272/30/33. Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) were used to evaluate the contouring accuracy. Contouring times were recorded for efficiency comparison. RESULTS: The mean DSC, MSD, and HD values for our DL-based tool were 0.88/1.32 mm/21.60 mm for dCTV1, 0.70/2.42 mm/22.44 mm for dCTV2, and 0.86/1.15 mm/20.78 mm for pCTV1. Only minor modifications were needed for 63.5% of auto-segmentations to meet the clinical requirements. The contouring accuracy of the DL-based tool was comparable to that of senior radiation oncologists and was superior to that of junior/intermediate radiation oncologists. Additionally, DL assistance improved the performance of junior radiation oncologists for dCTV2 and pCTV1 contouring (mean DSC increases: 0.20 for dCTV2, 0.03 for pCTV1; mean contouring time decrease: 9.8 min for dCTV2, 28.9 min for pCTV1). CONCLUSIONS: DL-based auto-segmentation improves CTV contouring accuracy, reduces contouring time, and improves clinical efficiency for treating cervical cancer.

DNA methylation biomarkers for diagnosis of primary liver cancer and distinguishing hepatocellular carcinoma from intrahepatic cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common pathology subtypes of primary liver cancer (PLC). Identifying DNA methylation biomarkers for diagnosis of PLC and further distinguishing HCC from ICC plays a vital role in subsequent treatment options selection. To obtain potential diagnostic DNA methylation sites for PLC, differentially methylated CpG (DMC) sites were first screened by comparing the methylation data between normal liver samples and PLC samples (ICC samples and HCC samples). A random forest algorithm was then used to select specific DMC sites with top Gini value. To avoid overfitting, another cohort was taken as an external validation for evaluating the area under curves (AUCs) of different DMC sites combination. A similar model construction strategy was applied to distinguish HCC from ICC. In addition, we identified DNA Methylation-Driven Genes in HCC and ICC via MethylMix method and performed pathway analysis by utilizing MetaCore. Finally, we not only performed methylator phenotype based on independent prognostic sites but also analyzed the correlations between methylator phenotype and clinical factors in HCC and ICC, respectively. To diagnose PLC, we developed a model based on three PLC-specific methylation sites (cg24035245, cg21072795, and cg00261162), whose sensitivity and specificity achieved 98.8%,94.8% in training set and 97.3%,81% in validation set. Then, to further divide the PLC samples into HCC and ICC, we established another mode through three methylation sites (cg17769836, cg17591574, and cg07823562), HCC accuracy and ICC accuracy achieved 95.8%, 89.8% in the training set and 96.8%,85.4% in the validation set. In HCC, the enrichment pathways were mainly related to protein folding, oxidative stress, and glutathione metabolism. While in ICC, immune response, embryonic hepatocyte maturation were the top pathways. Both in HCC and ICC, methylator phenotype correlated well with overall survival time and clinical factors involved in tumor progression. In summary, our study provides the biomarkers based on methylation sites not only for the diagnosis of PLC but also for distinguishing HCC from ICC.