Effective Non-Radiative Interfacial Recombination Suppression Scenario Using Air Annealing for Antimony Triselenide Thin-Film Solar Cells.

Antimony triselenide (Sb2Se3) has become a very promising candidate for next-generation thin-film solar cells due to the merits of their low-cost, low-toxic and excellent optoelectronic properties. Despite Sb2Se3 thin-film photovoltaic technology having undergone rapid development over the past few years, insufficient doping concentration and severe recombination have been the most challenging limitations hindering further breakthroughs for the Sb2Se3 solar cells. Post-annealing treatment of the Sb2Se3/CdS heterojunction was demonstrated to be very helpful in improving the device performance previously. In this work, post-annealing treatments were applied to the Sb2Se3/CdS heterojunction under a vacuum and in the air, respectively. It was found that compared to the vacuum annealing scenario, the air-annealed device presented notable enhancements in open-circuit voltage. Ultimately a competitive power conversion efficiency of 7.62% was achieved for the champion device via air annealing. Key photovoltaic parameters of the Sb2Se3 solar cells were measured and the effects of post-annealing treatments using different scenarios on the devices were discussed.

GWO+RuleFit: rule-based explainable machine-learning combined with heuristics to predict mid-treatment FDG PET response to chemoradiation for locally advanced non-small cell lung cancer.

OBJECTIVE: Vital rules learned from FDG-PET radiomics of tumor subregional response can provide clinical decision support for precise treatment adaptation. We combined a rule-based machine learning (ML) model (RuleFit) with a heuristic algorithm (Gray Wolf Optimizer, GWO) for mid-chemoradiation FDG-PET response prediction in patients with locally advanced non-small cell lung cancer. Approach: Tumors subregions were identified using K-means clustering. GWO+RuleFit consists of three main parts: (i) a random forest is constructed based on conventional features or radiomic features extracted from tumor regions or subregions in FDG-PET images, from which the initial rules are generated; (ii) GWO is used for iterative rule selection; (iii) the selected rules are fit to a linear model to make predictions about the target variable. Two target variables were considered: a binary response measure (∆SUVmean⩾20% decline) for classification and a continuous response measure (∆SUVmean) for regression. GWO+RuleFit was benchmarked against common ML algorithms and RuleFit, with leave-one-out cross-validated performance evaluated by the area under the receiver operating characteristic curve (AUC) in classification and root-mean-square error (RMSE) in regression. Main results: GWO+RuleFit selected 15 rules from the radiomic feature dataset of 23 patients. For treatment response classification, GWO+RuleFit attained numerically better cross-validated performance than RuleFit across tumor regions and sets of features (AUC:0.58-0.86 vs. 0.52-0.78, p=0.170-0.925). GWO+Rulefit also had the best or second-best performance numerically compared to all other algorithms for all conditions. For treatment response regression prediction, GWO+RuleFit (RMSE:0.162-0.192) performed better numerically for low-dimensional models (p=0.097-0.614) and significantly better for high-dimensional models across all tumor regions except one (RMSE:0.189-0.219, p<0.004). Significance: The GWO+RuleFit selected rules were interpretable, highlighting distinct radiomic phenotypes that modulated treatment response. GWO+Rulefit achieved parsimonious models while maintaining utility for treatment response prediction, which can aid clinical decisions for patient risk stratification, treatment selection, and biologically driven adaptation. Clinical trial: NCT02773238.

E3 ubiquitin ligase UBR5 modulates circadian rhythm by facilitating the ubiquitination and degradation of the key clock transcription factor BMAL1.

The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification level, offering potential insights into the modulation of the dysregulated circadian rhythm.

Overcoming Cancer Multi-drug Resistance (MDR): Reasons, mechanisms, nanotherapeutic solutions, and challenges.

Multi-drug resistance (MDR) in cancer cells, either intrinsic or acquired through various mechanisms, significantly hinders the therapeutic efficacy of drugs. Typically, the reduced therapeutic performance of various drugs is predominantly due to the inherent over expression of ATP-binding cassette (ABC) transporter proteins on the cell membrane, resulting in the deprived uptake of drugs, augmenting drug detoxification, and DNA repair. In addition to various physiological abnormalities and extensive blood flow, MDR cancer phenotypes exhibit improved apoptotic threshold and drug efflux efficiency. These severe consequences have substantially directed researchers in the fabrication of various advanced therapeutic strategies, such as co-delivery of drugs along with various generations of MDR inhibitors, augmented dosage regimens and frequency of administration, as well as combinatorial treatment options, among others. In this review, we emphasize different reasons and mechanisms responsible for MDR in cancer, including but not limited to the known drug efflux mechanisms mediated by permeability glycoprotein (P-gp) and other pumps, reduced drug uptake, altered DNA repair, and drug targets, among others. Further, an emphasis on specific cancers that share pathogenesis in executing MDR and effluxed drugs in common is provided. Then, the aspects related to various nanomaterials-based supramolecular programmable designs (organic- and inorganic-based materials), as well as physical approaches (light- and ultrasound-based therapies), are discussed, highlighting the unsolved issues and future advancements. Finally, we summarize the review with interesting perspectives and future trends, exploring further opportunities to overcome MDR.

Polymeric microcarriers for minimally-invasive cell delivery.

Tissue engineering (TE) aims at restoring tissue defects by applying the three-dimensional (3D) biomimetic pre-formed scaffolds to restore, maintain, and enhance tissue growth. Broadly speaking, this approach has created a potential impact in anticipating organ-building, which could reduce the need for organ replacement therapy. However, the implantation of such cell-laden biomimetic constructs based on substantial open surgeries often results in severe inflammatory reactions at the incision site, leading to the generation of a harsh adverse environment where cell survival is low. To overcome such limitations, micro-sized injectable modularized units based on various biofabrication approaches as ideal delivery vehicles for cells and various growth factors have garnered compelling interest owing to their minimally-invasive nature, ease of packing cells, and improved cell retention efficacy. Several advancements have been made in fabricating various 3D biomimetic microscale carriers for cell delivery applications. In this review, we explicitly discuss the progress of the microscale cell carriers that potentially pushed the borders of TE, highlighting their design, ability to deliver cells and substantial tissue growth in situ and in vivo from different viewpoints of materials chemistry and biology. Finally, we summarize the perspectives highlighting current challenges and expanding opportunities of these innovative carriers.

Roles of lipid metabolism and its regulatory mechanism in idiopathic pulmonary fibrosis: A review.

Idiopathic pulmonary fibrosis is a progressive lung disease of unknown etiology characterized by distorted distal lung architecture, inflammation, and fibrosis. Several lung cell types, including alveolar epithelial cells and fibroblasts, have been implicated in the development and progression of fibrosis. However, the pathogenesis of idiopathic pulmonary fibrosis is still incompletely understood. The latest research has found that dysregulation of lipid metabolism plays an important role in idiopathic pulmonary fibrosis. The changes in the synthesis and activity of fatty acids, cholesterol and other lipids seriously affect the regenerative function of alveolar epithelial cells and promote the transformation of fibroblasts into myofibroblasts. Mitochondrial function is the key to regulating the metabolic needs of a variety of cells, including alveolar epithelial cells. Sirtuins located in mitochondria are essential to maintain mitochondrial function and cellular metabolic homeostasis. Sirtuins can maintain normal lipid metabolism by regulating respiratory enzyme activity, resisting oxidative stress, and protecting mitochondrial function. In this review, we aimed to discuss the difference between normal and idiopathic pulmonary fibrosis lungs in terms of lipid metabolism. Additionally, we highlight recent breakthroughs on the effect of abnormal lipid metabolism on idiopathic pulmonary fibrosis, including the effects of sirtuins. Idiopathic pulmonary fibrosis has its high mortality and limited therapeutic options; therefore, we believe that this review will help to develop a new therapeutic direction from the aspect of lipid metabolism in idiopathic pulmonary fibrosis.

Efficacy and safety of immune checkpoint inhibitors in post-TKI NSCLC patients harboring EGFR mutations.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have been validated in epidermal growth factor receptor (EGFR) wild-type advanced non-small cell lung cancer (NSCLC) patients. However, there exists no evidence regarding NSCLC patients harboring EGFR mutations, experiencing EGFR-TKI (tyrosine kinase inhibitor) treatment failure. We collected clinical information from real world and conducted a time series-based meta-analysis to determine the efficacy and safety of ICIs in patients harboring EGFR mutations and experienced EGFR-TKIs resistance. METHODS: Twenty-two NSCLC patients with EGFR mutations after TKI resistance were included from two hospitals. PubMed, Embase and Cochrane Library were searched for relevant literature published until December 31, 2021. Endpoint outcomes included mortality and progression-free survival (PFS) at different times of follow-up. RESULTS: In total, 22 patients showed that the median PFS was 5.6 months (range 2.0-9.0 months). According to treatment strategies, the median PFS was 2.4 months (range 2.0-5.3 months) in the ICI monotherapy group and 5.9 months (range 2.8-9.0 months) in the ICI combined Chemotherapy group. Additionally, sixteen studies, including 5 trials, 10 controlled cohorts and 1 real-world study, were assessed, involving a total of ICI-treated NSCLC patients with EGFR mutation after TKI failure. The 6-month survival and PFS rate were 0.82 (95% CI 0.36-0.97) and 0.55 (95% CI 0.34-0.74), respectively. ICI combined chemotherapy showed the best survival outcome among these groups, as demonstrated by the 12-month survival rate and PFS. No new safety signals were identified with the combination therapy. The frequency of treatment-related adverse events was similar to that in previously reported studies of chemotherapy combined with checkpoint inhibitors. CONCLUSIONS: The addition of ICIs plus chemotherapy may significantly improve progression-free survival among patients with locally advanced or metastatic non-squamous NSCLC who EGFR-TKIs resistance.

Gradient Boosted Trees for Spatial Data and Its Application to Medical Imaging Data.

Boosting Trees are one of the most successful statistical learning approaches that involve sequentially growing an ensemble of simple regression trees ("weak learners"). This paper proposes a gradient Boosted Trees algorithm for Spatial Data (Boost-S) with covariate information. Boost-S integrates the spatial correlation into the classical framework of eXtreme Gradient Boosting. Each tree is constructed by solving a regularized optimization problem, where the objective function takes into account the underlying spatial correlation and involves two penalty terms on tree complexity. A computationally-efficient greedy heuristic algorithm is proposed to obtain an ensemble of trees. The proposed Boost-S is applied to the spatially-correlated FDG-PET (fluorodeoxyglucose-positron emission tomography) imaging data collected from clinical trials of cancer chemoradiotherapy. Our numerical investigations successfully demonstrate the advantages of the proposed Boost-S over existing approaches for this particular application.

SENP1 regulates the transformation of lung resident mesenchymal stem cells and is associated with idiopathic pulmonary fibrosis progression.

BACKGROUND: Lung resident mesenchymal stem cells (LR-MSCs) play an important role in idiopathic pulmonary fibrosis (IPF) by transforming into myofibroblasts, thereby losing their repair ability. Evidence suggests that key proteins of multiple signaling pathways are involved in myofibroblast differentiation of LR-MSCs, such as ß-Catenin and GLI family zinc finger 1 (GLI1). These proteins are regulated by SUMO (small ubiquitin-like modifier) modification, which is a post-translational modification that promotes protein degradation, while Sumo specific protein 1 (SENP1)-mediated deSUMOylation produces the opposite biological effects. Therefore, we speculated that SENP1 might be a potential target for treating pulmonary fibrosis by preventing the myofibroblast differentiation of LR-MSCs. METHODS: LR-MSCs were isolated from mice by using immunomagnetic beads. The extracted LR-MSCs were identified by flow cytometric analysis and multilineage differentiation assays. Lentivirus packaged shRNA silenced the expression of SENP1 in vitro and vivo. The silencing efficacy of SENP1 was verified by real-time quantitative PCR. The effect of down-regulated SENP1 on the myofibroblast differentiation of LR-MSCs was assessed by Immunofluorescence and Western blot. Immunoprecipitation was used to clarify that SENP1 was a key target for regulating the activity of multiple signaling pathways in the direction of LR-MSCs differentiation. LR-MSCs resident in the lung was analyzed with in vivo imaging system. HE and Masson staining was used to evaluate the therapeutic effect of LR-MSCs with SENP1 down-regulation on the lung of BLM mice. RESULTS: In this study, we found that the myofibroblast differentiation of LR-MSCs in IPF lung tissue was accompanied by enhanced SENP1-mediated deSUMOylation. The expression of SENP1 increased in LR-MSCs transition of bleomycin (BLM)-induced lung fibrosis. Interfering with expression of SENP1 inhibited the transformation of LR-MSCs into myofibroblasts in vitro and in vivo and restored their therapeutic effect in BLM lung fibrosis. In addition, activation of the WNT/ß-Catenin and Hedgehog/GLI signaling pathways depends on SENP1-mediated deSUMOylation. CONCLUSIONS: SENP1 might be a potential target to restore the repair function of LR-MSCs and treat pulmonary fibrosis. Video Abstract.

Multitask Learning Radiomics on Longitudinal Imaging to Predict Survival Outcomes following Risk-Adaptive Chemoradiation for Non-Small Cell Lung Cancer.

Medical imaging provides quantitative and spatial information to evaluate treatment response in the management of patients with non-small cell lung cancer (NSCLC). High throughput extraction of radiomic features on these images can potentially phenotype tumors non-invasively and support risk stratification based on survival outcome prediction. The prognostic value of radiomics from different imaging modalities and time points prior to and during chemoradiation therapy of NSCLC, relative to conventional imaging biomarker or delta radiomics models, remains uncharacterized. We investigated the utility of multitask learning of multi-time point radiomic features, as opposed to single-task learning, for improving survival outcome prediction relative to conventional clinical imaging feature model benchmarks. Survival outcomes were prospectively collected for 45 patients with unresectable NSCLC enrolled on the FLARE-RT phase II trial of risk-adaptive chemoradiation and optional consolidation PD-L1 checkpoint blockade (NCT02773238). FDG-PET, CT, and perfusion SPECT imaging pretreatment and week 3 mid-treatment was performed and 110 IBSI-compliant pyradiomics shape-/intensity-/texture-based features from the metabolic tumor volume were extracted. Outcome modeling consisted of a fused Laplacian sparse group LASSO with component-wise gradient boosting survival regression in a multitask learning framework. Testing performance under stratified 10-fold cross-validation was evaluated for multitask learning radiomics of different imaging modalities and time points. Multitask learning models were benchmarked against conventional clinical imaging and delta radiomics models and evaluated with the concordance index (c-index) and index of prediction accuracy (IPA). FDG-PET radiomics had higher prognostic value for overall survival in test folds (c-index 0.71 [0.67, 0.75]) than CT radiomics (c-index 0.64 [0.60, 0.71]) or perfusion SPECT radiomics (c-index 0.60 [0.57, 0.63]). Multitask learning of pre-/mid-treatment FDG-PET radiomics (c-index 0.71 [0.67, 0.75]) outperformed benchmark clinical imaging (c-index 0.65 [0.59, 0.71]) and FDG-PET delta radiomics (c-index 0.52 [0.48, 0.58]) models. Similarly, the IPA for multitask learning FDG-PET radiomics (30%) was higher than clinical imaging (26%) and delta radiomics (15%) models. Radiomics models performed consistently under different voxel resampling conditions. Multitask learning radiomics for outcome modeling provides a clinical decision support platform that leverages longitudinal imaging information. This framework can reveal the relative importance of different imaging modalities and time points when designing risk-adaptive cancer treatment strategies.

Wiltse Approach Versus Conventional Transforaminal Interbody Fusion for Unstable Thoracolumbar Fracture with Intervertebral Disc Lesions.

OBJECTIVE: To compare the clinical results of two surgical techniques, Wiltse approach and conventional transforaminal interbody fusion, for the treatment of unstable thoracolumbar fracture associated with traumatic intervertebral disc lesion (TIDL). METHODS: A total of 76 patients with unstable thoracolumbar fracture associated with TIDL treated by posterior pedicle screw fixation and transforaminal thoracolumbar interbody fusion from June 2010 and July 2016 were reviewed retrospectively. These patients including 48 male and 28 female patients were divided into Wiltse approach transforaminal thoracolumbar interbody fusion (W-TLIF) group (n = 38) and conventional transforaminal thoracolumbar interbody fusion (C-TLIF) group (n = 38). Patients were followed up for about 33 months. Clinical and radiological records, kyphotic angle, fractured vertebral body height, visual analogue score (VAS), Oswestry Disability Index (ODI), complications, neurological improvement and fusion rate were compared between two groups. RESULTS: All patients underwent posterior surgery successfully. Blood loss, operation time and hospital stay in the W-TLIF group was 437.84 ± 143.98 ml, 118.64 ± 20.55 min and 12.32 ± 2.87 days, respectively. While those parameters in the C-TLIF group was 862.70 ± 300.24 ml, 141.35 ± 31.72 min and 15.51 ± 2.08 days, respectively. Average operation time and hospital stay time were significantly shorter, and blood loss was significantly less in the W-TLIF group than in the C-TLIF group (P < 0.05). VAS and ODI in the W-TLIF group were significantly less than those in the C-TLIF group at 1 week after operation and final follow-up. The kyphotic angle and vertebral body height were improved. There was 1-2 grade improvement in patients with neurological deficit. Thirty-three patients in the W-TLIF group and 32 patients in the C-TLIF group had achieved fusion during follow-up. No internal fixation failure was observed in two groups. CONCLUSIONS: The both techniques of W-TLIF and C-TLIF were feasible and effective for unstable thoracolumbar fracture with TIDL. Compare to C-TLIF, The technique of W-TLIF was a relatively less invasive way to decompress the neural elements and an easy method to reconstruct the anterior column using the same posterior approach.

KL-6 as an Immunological Biomarker Predicts the Severity, Progression, Acute Exacerbation, and Poor Outcomes of Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

Object: Interstitial lung disease (ILD) is a specific form of chronic fibrosing interstitial pneumonia with various etiology. The severity and progression of ILD usually predict the poor outcomes of ILD. Otherwise, Krebs von den Lungen-6 (KL-6) is a potential immunological biomarker reflecting the severity and progression of ILD. This meta-analysis is to clarify the predictive value of elevated KL-6 levels in ILD. Method: EBSCO, PubMed, and Cochrane were systematically searched for articles exploring the prognosis of ILD published between January 1980 and April 2021. The Weighted Mean Difference (WMD) and 95% Confidence Interval (CI) were computed as the effect sizes for comparisons between groups. For the relationship between adverse outcome and elevated KL-6 concentration, Hazard Ratio (HR), and its 95%CI were used to estimate the risk factor of ILD. Result: Our result showed that ILD patients in severe and progressive groups had higher KL-6 levels, and the KL-6 level of patients in the severe ILD was 703.41 (U/ml) than in mild ILD. The KL-6 level in progressive ILD group was 325.98 (U/ml) higher than that in the non-progressive ILD group. Secondly, the KL-6 level of patients in acute exacerbation (AE) of ILD was 545.44 (U/ml) higher than stable ILD. Lastly, the higher KL-6 level in ILD patients predicted poor outcomes. The KL-6 level in death of ILD was 383.53 (U/ml) higher than in survivors of ILD. The pooled HR (95%CI) about elevated KL-6 level predicting the mortality of ILD was 2.05 (1.50-2.78), and the HR (95%CI) for progression of ILD was 1.98 (1.07-3.67). Conclusion: The elevated KL-6 level indicated more severe, more progressive, and predicted the higher mortality and poor outcomes of ILD.

Ferroptosis-mediated Crosstalk in the Tumor Microenvironment Implicated in Cancer Progression and Therapy.

Ferroptosis is a recently recognized form of non-apoptotic regulated cell death and usually driven by iron-dependent lipid peroxidation and has arisen to play a significant role in cancer biology. Distinct from other types of cell death in morphology, genetics, and biochemistry, ferroptosis is characterized by the accumulation of lipid peroxides and lethal reactive oxygen species controlled by integrated oxidant and antioxidant systems. Increasing evidence indicates that a variety of biological processes, including amino acid, iron, lactate, and lipid metabolism, as well as glutathione, phospholipids, NADPH, and coenzyme Q10 biosynthesis, are closely related to ferroptosis sensitivity. Abnormal ferroptotic response may modulate cancer progression by reprogramming the tumor microenvironment (TME). The TME is widely associated with tumor occurrence because it is the carrier of tumor cells, which interacts with surrounding cells through the circulatory and the lymphatic system, thus influencing the development and progression of cancer. Furthermore, the metabolism processes play roles in maintaining the homeostasis and evolution of the TME. Here, this review focuses on the ferroptosis-mediated crosstalk in the TME, as well as discussing the novel therapeutic strategies for cancer treatment.

Complete chloroplast genome characteristics of Prunus triloba Lindl.

Prunus triloba Lindl. is a small shrub species, with many varieties and a long history of cultivation. It has been widely used for landscaping and is grown as a traditional flowering tree species in northern China. In this study, we sequenced the P. triloba Lindl. chloroplast genome, which forms a circular structure comprising 158,455 bp, including a pair of inverted repeat regions (52,634 bp), a large single-copy region (86,386 bp), and a small single-copy region (19,028 bp). We annotated 131 genes, including 86 coding sequences, 8 rRNA sequences, and 37 tRNA sequences. Furthermore, a phylogenetic analysis revealed P. triloba Lindl. is closely related to Prunus pedunculata.

GSK­3ß inhibition promotes doxorubicin­induced apoptosis in human cholangiocarcinoma cells via FAK/AKT inhibition.

Cholangiocarcinoma (CCA) is the most common type of malignant tumor of the bile duct and is characterized by high morbidity and mortality; it is difficult to diagnose in the early stages and responds poorly to current conventional radiotherapy and chemotherapy. The present study investigated the role of GSK­3ß signaling on the anticancer effects of doxorubicin in human CCA cells. Blocking GSK­3ß enhanced the sensitivity of human CCA cells to doxorubicin (Dox)­induced apoptosis, which was accompanied by decreased AKT and focal adhesion kinase (FAK) activity. Moreover, inhibiting GSK­3ß using 6­bromoindirubin­3'­oxime, CHIR99021 or small interfering RNA decreased phosphorylation of FAK and AKT, and promoted apoptosis of Dox­induced human CCA cells. Moreover, FAK inhibition suppressed AKT activity independently of phosphoinositide 3­kinase activity. These results indicated that GSK­3ß protects human CCA cells against Dox­induced apoptosis via sustaining FAK/AKT activity.

Sensitivity analysis of FDG PET tumor voxel cluster radiomics and dosimetry for predicting mid-chemoradiation regional response of locally advanced lung cancer.

We investigated the sensitivity of regional tumor response prediction to variability in voxel clustering techniques, imaging features, and machine learning algorithms in 25 patients with locally advanced non-small cell lung cancer (LA-NSCLC) enrolled on the FLARE-RT clinical trial. Metabolic tumor volumes (MTV) from pre-chemoradiation (PETpre) and mid-chemoradiation fluorodeoxyglucose-positron emission tomography (FDG PET) images (PETmid) were subdivided into K-means or hierarchical voxel clusters by standardized uptake values (SUV) and 3D-positions. MTV cluster separability was evaluated by CH index, and morphologic changes were captured by Dice similarity and centroid Euclidean distance. PETpre conventional features included SUVmean, MTV/MTV cluster size, and mean radiation dose. PETpre radiomics consisted of 41 intensity histogram and 3D texture features (PET Oncology Radiomics Test Suite) extracted from MTV or MTV clusters. Machine learning models (multiple linear regression, support vector regression, logistic regression, support vector machines) of conventional features or radiomic features were constructed to predict PETmid response. Leave-one-out-cross-validated root-mean-squared-error (RMSE) for continuous response regression (ΔSUVmean) and area-under-receiver-operating-characteristic-curve (AUC) for binary response classification were calculated. K-means MTV 2-clusters (MTVhi, MTVlo) achieved maximum CH index separability (Friedman p < 0.001). Between PETpre and PETmid, MTV cluster pairs overlapped (Dice 0.70-0.87) and migrated 0.6-1.1 cm. PETmid ΔSUVmean response prediction was superior in MTV and MTVlo (RMSE = 0.17-0.21) compared to MTVhi (RMSE = 0.42-0.52, Friedman p < 0.001). PETmid ΔSUVmean response class prediction performance trended higher in MTVlo (AUC = 0.83-0.88) compared to MTVhi (AUC = 0.44-0.58, Friedman p = 0.052). Models were more sensitive to MTV/MTV cluster regions (Friedman p = 0.026) than feature sets/algorithms (Wilcoxon signed-rank p = 0.36). Top-ranked radiomic features included GLZSM-LZHGE (large-zone-high-SUV), GTSDM-CP (cluster-prominence), GTSDM-CS (cluster-shade) and NGTDM-CNT (contrast). Top-ranked features were consistent between MTVhi and MTVlo cluster pairs but varied between MTVhi-MTVlo clusters, reflecting distinct regional radiomic phenotypes. Variability in tumor voxel cluster response prediction can inform robust radiomic target definition for risk-adaptive chemoradiation in patients with LA-NSCLC. FLARE-RT trial: NCT02773238.

Percutaneous intervertebral bridging cementoplasty for adjacent multilevel osteoporotic thoracolumbar fractures with vertebral endplate-disc complex injury: technical note.

This paper describes a minimally invasive technique of percutaneous intervertebral bridging cementoplasty (PIBC) to augment the fractured vertebrae and immobilize the intervertebral space with endplate-disc complex injury simultaneously. Thirty-two patients with adjacent multilevel osteoporotic thoracolumbar fractures (AMOTLFs) and vertebral endplate-disc complex injury (EDCI) treated by PIBC were retrospectively reviewed. The PIBC technique was a combination of puncture, balloon expansion and bridging cementoplasty. The clinical and radiological assessments were reviewed. The operation time was 82.8 ± 32.5 min, and blood loss was 76.9 ± 31.7 mL. A cement bridge was connected between the two fractured vertebrae across the injured intervertebral space. VAS at three time points including pre-operation, post-operation 1 day and final follow-up was 6.9 ± 0.9, 2.9 ± 0.8 and 1.7 ± 0.8, respectively; ODI at three time points was (71.1 ± 7.8)%, (18.4 ± 5.7)%, and (10.3 ± 5.7)%, respectively; Cobb angle at three time points was 46.0° ± 10.4°, 25.9° ± 8.5°, and 27.5° ± 7.1°, respectively. Compared with pre-operation, VAS, ODI and Cobb angle were significantly improved at post-operation 1 day and final follow-up (P < 0.05). Clinical asymptomatic cement leakage was observed in thirteen patients. No vessel or neurological injury was observed. PIBC may be an alternative way of treatment for AMOTLFs with EDCI. The technique is a minimally invasive surgery to augment the fractured vertebrae and immobilize the injured intervertebral space simultaneously.

Correction: Two-dimensional nanocoating-enabled orthopedic implants for bimodal therapeutic applications.

Correction for 'Two-dimensional nanocoating-enabled orthopedic implants for bimodal therapeutic applications' by Song Wang et al., Nanoscale, 2020, 12, 11936-11946, DOI: 10.1039/D0NR02327B.

Two-dimensional nanocoating-enabled orthopedic implants for bimodal therapeutic applications.

As one of the promising orthopedic materials, polyetheretherketone (PEEK) has high chemical durability and similar mechanical properties to the cortical bone; nevertheless, the inherent bioinert nature of PEEK dramatically impedes its broader clinical applications in the management of bone infection. To address this challenge, herein, we developed a multifunctional two-dimensional (2D) nanocoating to assemble graphene oxide (GO) nanosheets, a polydopamine (pDA) nanofilm, and an oligopeptide onto the surface of porous sulfonated PEEK (SPEEK). The resulting multifunctional PEEK implants exhibited enhanced cytocompatibility, alkaline phosphatase activity, and calcium matrix deposition as well as osteogenesis-associated gene expression. Moreover, the animal experiments based on a rabbit femur defect model confirmed that the 2D nanocoating prominently boosted the in vivo osseointegration and bone remodeling. Besides, the GO/pDA hybrid complex anchoring on the SPEEK surface through π-π stacking can generate robust antibacterial phototherapy resulting from the synergetic photothermal/photodynamic therapeutic effects. Accordingly, this work provides a paradigm to empower inert PEEK implants with bi-/multi-modal therapeutic applications, such as against bone infection treatment.