Pneumonitis After Concurrent Chemoradiation and Immune Checkpoint Inhibition in Patients with Locally Advanced Non-small Cell Lung Cancer.

AIMS: Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival. MATERIALS AND METHODS: We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality. RESULTS: The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality. CONCLUSIONS: Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.

Three-Dimensional Printed Highly Porous and Flexible Conductive Polymer Nanocomposites with Dual-Scale Porosity and Piezoresistive Sensing Functions.

Highly flexible, deformable, and ultralightweight structures are required for advanced sensing applications, such as wearable electronics and soft robotics. This study demonstrates the three-dimensional (3D) printing of highly flexible, ultralightweight, and conductive polymer nanocomposites (CPNCs) with dual-scale porosity and piezoresistive sensing functions. Macroscale pores are established by designing structural printing patterns with adjustable infill densities, while the microscale pores are developed by phase separation of the deposited polymer ink solution. A conductive polydimethylsiloxane solution is prepared by mixing polymer/carbon nanotubes with non-solvent and solvent phases. Silica nanoparticles are utilized to modify the rheological properties of the ink, making direct ink writing (DIW) feasible. 3D geometries with various structural infill densities and polymer concentrations are deposited using DIW. The solvent is evaporated during a stepping heat treatment, leading to non-solvent droplet nucleation and growth. The microscale cellular network is developed by removing the droplets and curing the polymer. Up to 83% tunable porosity is achieved by independently controlling the macro- and microscale porosity. The effect of macroscale/microscale porosity and printing nozzle sizes on the mechanical and piezoresistive behavior of the CPNC structures is explored. The electrical and mechanical tests demonstrate a durable, extremely deformable, and sensitive piezoresistive response without sacrificing mechanical performance. The flexibility and sensitivity of the CPNC structure are enhanced up to 900 and 67% with the development of dual-scale porosity. The application of the developed porous CPNCs as piezoresistive sensors for detecting human motion is also evaluated.

Funnel-Shaped Floating Vessel Oil Skimmer with Joule Heating Sorption Functionality.

Floating vessel-type oil collecting devices based on sorbent materials present potential solutions to oil spill cleanup that require a massive amount of sorbent material and manual labor. Additionally, continuous oil extraction from these devices presents opportunities for highly energy-efficient oil skimmers that use gravity as the oil/water separation mechanism. Herein, a sorbent-based oil skimmer (SOS) is developed with a novel funnel-shaped sorbent and vessel design for efficient and continuous extraction of various oils from the water surface. A carbon black (CB) embedded polydimethylsiloxane (PDMS) sponge material is characterized and used as the sorbent in the SOS. The nanocomposite sponge formulation is optimized for high reusability, hydrophobicity, and rapid oil absorption. Joule heating functionality of the sponge is also explored to rapidly absorb highly viscous oils that are a significant challenge for oil spill cleanup. The optimized sponge material with the highest porosity and 15 wt% CB loading is tested in the SOS for large-scale oil spill extraction tests and shows effective cleaning of oil spilled on the water surface. The SOS demonstrates a high maximum extraction rate of 200 mL/min for gasoline and maintains a high extraction rate performance upon reuse when the sponge funnel is cleaned and dried.

Synthesis, Characterization, and Modeling of Aligned ZnO Nanowire-Enhanced Carbon-Fiber-Reinforced Composites.

This paper presents the synthesis, characterization, and multiscale modeling of hybrid composites with enhanced interfacial properties consisting of aligned zinc oxide (ZnO) nanowires and continuous carbon fibers. The atomic layer deposition method was employed to uniformly synthesize nanoscale ZnO seeds on carbon fibers. Vertically aligned ZnO nanowires were grown from the deposited nanoscale seeds using the low-temperature hydrothermal method. Morphology and chemical compositions of ZnO nanowires were characterized to evaluate the quality of synthesized ZnO nanowires in hybrid fiber-reinforced composites. Single fiber fragmentation tests reveal that the interfacial shear strength (IFSS) in epoxy composites improved by 286%. Additionally, a multiscale modeling framework was developed to investigate the IFSS of hybrid composites with radially aligned ZnO nanowires. The cohesive zone model (CZM) was implemented to model the interface between fiber and matrix. The damage behavior of fiber was simulated using the ABAQUS user subroutine to define a material's mechanical behavior (UMAT). Both experimental and analytical results indicate that the hierarchical carbon fibers enhanced by aligned ZnO nanowires are effective in improving the key mechanical properties of hybrid fiber-reinforced composites.

Post-chemotherapy and targeted therapy imaging of the chest in lung cancer.

Non-small-cell lung cancer (NSCLC) is frequently diagnosed when it is not amenable to local therapies; therefore, systemic agents are the mainstay of therapy for many patients. In recent years, treatment of advanced NSCLC has evolved from a general approach primarily involving chemotherapy to a more personalised strategy in which biomarkers such as the presence of genomic tumour aberrations and the expression of immune proteins such as programmed death-ligand 1 (PD-L1), in combination with other elements of clinical information such as histology and clinical stage, guide management. For instance, pathways resulting in uncontrolled growth and proliferation of tumour cells due to epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements may be targeted by tyrosine kinase inhibitors (TKIs). In this article, we review the current state of medical oncology, imaging characteristics of mutations, pitfalls in response assessments and the imaging of complications.

Post-immunotherapy imaging in lung cancer.

By boosting the immune system, immunotherapy with immune checkpoint inhibitors (ICIs) has altered the management of patients with various cancers including those with metastatic non-small cell lung cancer (NSCLC). As a result of immune system activation, ICIs are associated with unique response patterns (that are not addressed by traditional response criteria) and inflammatory side effects termed immune-related adverse events. In this article, we will review the role of immunotherapy in cancer treatment, specifically ICIs used in NSCLC treatment, radiological response criteria of immunotherapy, and the imaging spectrum of immune-related adverse events.

PDMS Sponges with Embedded Carbon Nanotubes as Piezoresistive Sensors for Human Motion Detection.

Porous piezoresistive sensors offer promising flexible sensing functionality, such as human joint motion detection and gesture identification. Herein, a facile fabrication method is developed using a microwave-based rapid porogen removal technique for the manufacturing of porous nanocomposite sponges consisting of polydimethylsiloxane (PDMS) and well-dispersed carbon nanotubes (CNTs). The porogen amounts and CNT loadings are varied to tailor the porosity and electrical properties of the porous sensors. The sponges are characterized by a scanning electron microscope (SEM) to compare their microstructures, validate the high-quality CNT dispersion, and confirm the successful nanofiller embedding within the elastomeric matrix. Sponges with a 3 wt% CNT loading demonstrate the highest piezoresistive sensitivity. Experimental characterization shows that the sponges with low porosity have long durability and minimal strain rate dependence. Additionally, the developed sponges with 3 wt% CNTs are employed for the human motion detection using piezoresistive method. One experiment includes fingertip compression measurements on a prosthetic hand. Moreover, the sensors are attached to the chest, elbow, and knee of a user to detect breathing, running, walking, joint bending, and throwing motions.

Transcriptome analysis discloses dysregulated genes in normal appearing tumor-adjacent thyroid tissues from patients with papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The molecular characteristics of histologically normal appearing tissue adjacent to the tumor (NAT) from PTC patients are not well characterized. The aim of this study was to characterize the global gene expression profile of NAT and compare it with those of normal and tumor thyroid tissues. We performed total RNA sequencing with fresh frozen thyroid tissues from a cohort of three categories of samples including NAT, normal thyroid (N), and PTC tumor (T). Transcriptome analysis shows that NAT presents a unique gene expression profile, which was not associated with sex or the presence of lymphocytic thyroiditis. Among the differentially expressed genes (DEGs) of NAT vs N, 256 coding genes and 5 noncoding genes have been reported as cancer genes involved in cell proliferation, apoptosis, and/or tumorigenesis. Bioinformatics analysis with Ingenuity Pathway Analysis software revealed that "Cancer, Organismal Injury and Abnormalities, Cellular Response to Therapeutics, and Cellular Movement" were major dysregulated pathways in the NAT tissues. This study provides improved insight into the complexity of gene expression changes in the thyroid glands of patients with PTC.

Rapid Microwave Polymerization of Porous Nanocomposites with Piezoresistive Sensing Function.

In this paper, polydimethylsiloxane (PDMS) and multi-walled carbon nanotube (MWCNT) nanocomposites with piezoresistive sensing function were fabricated using microwave irradiation. The effects of precuring time on the mechanical and electrical properties of nanocomposites were investigated. The increased viscosity and possible nanofiller re-agglomeration during the precuring process caused decreased microwave absorption, resulting in extended curing times, and decreased porosity and electrical conductivity in the cured nanocomposites. The porosity generated during the microwave-curing process was investigated with a scanning electron microscope (SEM) and density measurements. Increased loadings of MWCNTs resulted in shortened curing times and an increased number of small well-dispersed closed-cell pores. The mechanical properties of the synthesized nanocomposites including stress-strain behaviors and Young's Modulus were examined. Experimental results demonstrated that the synthesized nanocomposites with 2.5 wt. % MWCNTs achieved the highest piezoresistive sensitivity with an average gauge factor of 7.9 at 10% applied strain. The piezoresistive responses of these nanocomposites were characterized under compressive loads at various maximum strains, loading rates, and under viscoelastic stress relaxation conditions. The 2.5 wt. % nanocomposite was successfully used in an application as a skin-attachable compression sensor for human motion detection including squeezing a golf ball.

Defining the adult hippocampal neural stem cell secretome: In vivo versus in vitro transcriptomic differences and their correlation to secreted protein levels.

Adult hippocampal neural stem and progenitor cells (NSPCs) secrete a variety of proteins that affect tissue function. Though several individual NSPC-derived proteins have been shown to impact key cellular processes, a broad characterization is lacking. Secretome profiling of low abundance stem cell populations is typically achieved via proteomic characterization of in vitro, isolated cells. Here, we identified hundreds of secreted proteins in conditioned media from in vitro adult mouse hippocampal NSPCs using an antibody array and mass spectrometry. Comparison of protein abundance between antibody array and mass spectrometry plus quantification of several key secreted proteins by ELISA revealed notable disconnect between methods in what proteins were identified as being high versus low abundance, suggesting that data from antibody arrays in particular should be approached with caution. We next assessed the NSPC secretome on a transcriptional level with single cell and bulk RNA sequencing (RNAseq) of cultured NSPCs. Comparison of RNAseq transcript levels of highly secreted proteins revealed that quantification of gene expression did not necessarily predict relative protein abundance. Interestingly, comparing our in vitro NSPC gene expression data with similar data from freshly isolated, in vivo hippocampal NSPCs revealed strong correlations in global gene expression between in vitro and in vivo NSPCs. Understanding the components and functions of the NSPC secretome is essential to understanding how these cells may modulate the hippocampal neurogenic niche. Cumulatively, our data emphasize the importance of using proteomics in conjunction with transcriptomics and highlights the need for better methods of unbiased secretome profiling.

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.

BACKGROUND: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. PATIENTS AND METHODS: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . RESULTS: Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. CONCLUSION: Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.

Three-Dimensional Nano-Morphology of Carbon Nanotube/Epoxy Filled Poly(methyl methacrylate) Microcapsules.

The three-dimensional nano-morphology of poly(methyl methacrylate; PMMA) microcapsules filled with carbon nanotubes (CNTs) and epoxy resin were investigated by various microscopy methods, including a novel, laser scanning confocal microscopy (LSCM) method. Initially, PMMA microcapsules containing various amounts of CNTs were synthesized by a solvent evaporation method. Scanning electron microscopy analysis showed that pore-free, smooth-surface microcapsules formed with various types of core-shell morphologies. The average size of CNT/epoxy/PMMA microcapsules was shown to decrease from ~52 µm to ~15 µm when mixing speed during synthesis increased from 300 rpm to 1000 rpm. In general, the presence of CNTs resulted in slightly larger microcapsules and higher variations in size. Moreover, three-dimensional scans obtained from confocal microscopy revealed that higher CNT content increased the occurrence and size of CNT aggregates inside the microcapsules. Entrapped submicron air bubbles were also observed inside most microcapsules, particularly within those with higher CNT content.

Surgical outcome of patients with vesicoureteral reflux from a single institution in reference to the ESPU guidelines: a retrospective analysis.

INTRODUCTION: Vesicoureteral reflux (VUR) is an anatomic or functional disorder, and it is a condition associated with renal scarring, hypertension, and end-stage renal disease. Renal damage can be prevented by appropriate medical and surgical intervention for selected patients. OBJECTIVES: The objective of this study was to retrospectively analyze the surgically treated patient group of this study in reference to the risk analysis criteria used in European Association of Urology (EAU), European Society for Paediatric Urology (ESPU) guidelines to see the outcome of the study management protocol within the last 15 years in respect to this risk analysis. STUDY DESIGN: A total of 686 patients who were operated upon in a single institution for VUR between 1997 and 2016 were retrospectively analyzed. According to the criteria in EAU/ESPU guidelines, the patients were classified into three groups: low, medium, and high risk. Risk factors were compared between the groups. RESULTS: The patient numbers for low, medium, and high risk were 92 (13.4%), 485 (70.7%), and 109 (15.9%), respectively. In the high-risk group, surgeons tended to do more ureteroneocystostomy (UNC) (82.6%), whereas in the low-risk group, surgeons tended to do more subureteric injection (STING) (76.1%). The success rates for STING and UNC were found to be 75% and 93%, respectively. Although there was a difference in success rates among patients treated with STING or UNC, this difference was not statistically significant in success rates regarding risk groups for patients treated with STING or UNC. DISCUSSION: The most recent guideline was that which was published by the EAU/ESPU organization in 2012. This guideline is established based on the risk analysis. The analysis revealed that patients in the low-risk group tended to undergo endoscopic surgery treatment method, whereas patients in the high-risk group tended to undergo open surgery. Therefore, the study management over the last 10 years has been mainly in line with the current recommendations. CONCLUSION: The analysis shows that when the patients are classified according to the EAU/ESPU risk classification, surgeons tended to perform more endoscopic and more open surgery for the low- and high-risk groups, respectively. Although each surgical modality had similar success rates in each group, open surgical results were overall much higher than those of endoscopic surgery in each group. This was a specifically important finding in high-risk group where the endoscopically treated group of patients was small in number, and the need for a definitive correction is essential in this group because of increased risk of renal injury.

Silk as a Natural Reinforcement: Processing and Properties of Silk/Epoxy Composite Laminates.

With growing environmental awareness, natural fibers have recently received significant interest as reinforcement in polymer composites. Among natural fibers, silk can potentially be a natural alternative to glass fibers, as it possesses comparable specific mechanical properties. In order to investigate the processability and properties of silk reinforced composites, vacuum assisted resin transfer molding (VARTM) was used to manufacture composite laminates reinforced with woven silk preforms. Specific mechanical properties of silk/epoxy laminates were found to be anisotropic and comparable to those of glass/epoxy. Silk composites even exhibited a 23% improvement of specific flexural strength along the principal weave direction over the glass/epoxy laminate. Applying 300 kPa external pressure after resin infusion was found to improve the silk/epoxy interface, leading to a discernible increase in breaking energy and interlaminar shear strength. Moreover, the effect of fabric moisture on the laminate properties was investigated. Unlike glass mats, silk fabric was found to be prone to moisture absorption from the environment. Moisture presence in silk fabric prior to laminate fabrication yielded slower fill times and reduced mechanical properties. On average, 10% fabric moisture induced a 25% and 20% reduction in specific flexural strength and modulus, respectively.

Magnet Assisted Composite Manufacturing: A Flexible New Technique for Achieving High Consolidation Pressure in Vacuum Bag/Lay-Up Processes.

This work demonstrates a protocol to improve the quality of composite laminates fabricated by wet lay-up vacuum bag processes using the recently developed magnet assisted composite manufacturing (MACM) technique. In this technique, permanent magnets are utilized to apply a sufficiently high consolidation pressure during the curing stage. To enhance the intensity of the magnetic field, and thus, to increase the magnetic compaction pressure, the magnets are placed on a magnetic top plate. First, the entire procedure of preparing the composite lay-up on a magnetic bottom steel plate using the conventional wet lay-up vacuum bag process is described. Second, placement of a set of Neodymium-Iron-Boron permanent magnets, arranged in alternating polarity, on the vacuum bag is illustrated. Next, the experimental procedures to measure the magnetic compaction pressure and volume fractions of the composite constituents are presented. Finally, methods used to characterize microstructure and mechanical properties of composite laminates are discussed in detail. The results prove the effectiveness of the MACM method in improving the quality of wet lay-up vacuum bag laminates. This method does not require large capital investment for tooling or equipment and can also be used to consolidate geometrically complex composite parts by placing the magnets on a matching top mold positioned on the vacuum bag.

Fabrication of High Quality, Large Wet Lay-Up/Vacuum Bag Laminates by Sliding a Magnetic Tool.

This study presents a novel method to fabricate high-quality, large composite parts which can be used in a wet lay-up/vacuum bag (WLVB) process. The new method utilizes a commercial lifting magnet, which is commonly used for transporting ferrous plates, to apply a magnetic consolidation pressure on the WLVB composite lay-up. The pressure is applied on a large area of the laminate by slowly sliding the magnet over the vacuum bag surface, which leads to an improved laminate quality. When further improvement is desirable, multiple passes of the magnet can be performed, where each pass successively compacts the lay-up. To explore the feasibility of implementing this technique, random mat and plain weave glass/epoxy laminates were fabricated, and their properties compared to conventional WLVB laminates. The effects of the number of moving passes of the lifting magnet on the laminate microstructure and properties are also investigated. As a result of multiple passes, the fiber volume fraction in random mat and plain weave laminates increases to 34% and 53%, representing 80% and 16% improvements, respectively. In addition, the void volume fraction reduces almost by 60% to a very low level of 0.7% and 1.1%, respectively. Consequently, the flexural properties considerably enhance by 20⁻81%, which demonstrates the potential of the proposed method to produce WLVB parts with substantially higher quality. It is also shown that there exists an optimal number of passes, depending on the fabric type where additional passes induce new voids as a result of excessive resin removal.

Percutaneous Nephrolithotomy in Children: 17 Years of Experience.

PURPOSE: We analyzed factors that might affect outcome in terms of success and incidence of complications in children up to 17 years after undergoing percutaneous nephrolithotomy. MATERIALS AND METHODS: The data of 346 renal units (294 patients) were analyzed in terms of postoperative outcome. Factors investigated that might affect outcome were patient gender, age, stone laterality, largest stone size, stone burden, number of stones, location of a single stone, previous intervention and instrument size. RESULTS: Mean ± SD patient age was 8.51 ± 4.91 years, and male-to-female ratio was 209:137. Mean ± SD stone burden was 3.49 ± 3.3 cm(2). Stone-free rates after a single procedure were 84.4% and 73.1% in patients with and without clinically insignificant residual stones, respectively. On univariate and multivariate analyses stone burden and number of stones affected the stone-free rate. Complications consisted of bleeding in 41 patients (11.8%), postoperative urinary tract infection in 21 (6%), urosepsis in 4 (0.1%) and hydrothorax in 4 (0.1%). One patient died of multiple organ failure. Through the years blood transfusion and complication rates decreased, and the use of smaller instruments increased significantly. Although bleeding occurred less often in cases where a 14Fr sheath was used rather than a larger sheath (5% vs 12%, p = 0.142), the difference was not significant. No significant factor affecting complication rates was detected. CONCLUSIONS: As in adults, percutaneous nephrolithotomy can be used in children with acceptable complication rates and good success rates for surgical treatment of complex renal stones. Number of stones and stone burden are predictive of postoperative stone-free rate.

Replication of human tracheobronchial hollow airway models using a selective laser sintering rapid prototyping technique.

Exposures to toxic or pathogenic aerosols are known to produce adverse health effects. The nature and severity of these effects often are governed in large part by the location and amount of aerosol deposition within the respiratory tract. Morphologically detailed replica hollow lung airway casts are widely used in aerosol deposition research; however, techniques are not currently available that allow replicate deposition studies in identical morphologically detailed casts produced from a common reference anatomy. This project developed a technique for the precision manufacture of morphologically detailed human tracheobronchial airway models based on high-resolution anatomical imaging data. Detailed physical models were produced using the selective laser sintering (SLS) rapid prototyping process. Input to the SLS process was a three-dimensional computer model developed by boundary-based two-dimension to three-dimension conversion of anatomical images from the original National Institutes of Health/National Library of Medicine Visible Human male data set. The SLS process produced identical replicate models that corresponded exactly to the anatomical section images, within the limits of the measurement. At least five airway generations were achievable, corresponding to airways less than 2 mm in diameter. It is anticipated that rapid prototyping manufacture of respiratory tract structures based on reference anatomies such as the Visible Male and Visible Female may provide "gold standard" models for inhaled aerosol deposition studies. Adaptations of the models to represent various disease states may be readily achieved, thereby promoting exploration of pharmaceutical research on targeted drug delivery via inhaled aerosols.