MUC4 O-GlcNAcylation Regulates the Epithelial Phenotype in Conjunctival Epithelial Cells.

In the present study, our aim was to explore the role of MUC4 in IL-4-stimulated conjunctival epithelial cells and the underlying mechanisms. Human recombinant IL-4 was employed in human conjunctival epithelial cells (HConEpic) cells, and MUC4 shRNA (sh-MUC4) was constructed to explore the functional role of MUC4. The protein level of MUC4, O-GlcNAc transferase (OGT), O-GlcNAc hydrolase (OGA), zonula occludens 1 (ZO-1), gap junction protein beta 2 (GJB2), claudin-8 (CLDN8), and E-cadherin were detected by Western blot in HConEpic cells, the interaction between MUC4 and OGT/OGA was assessed by co-immunoprecipitation (IP) and Western blot in 293T cells. Our results showed that IL-4 significantly up-regulated MUC4 and OGT protein levels in HConEpic cells, while down-regulated OGA protein level. Also, IL-4 down-regulated ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, while which was markedly reversed by sh-MUC4. Additionally, OGT inhibitor significantly reduced MUC4 protein level, and elevated ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, while OGA inhibitor resulted in the opposite results. Furthermore, in addition to the interaction between OGT/OGA and MUC4, Co-IP and Western blot also revealed the alteration of MUC4 O-GlcNAcylation in 293T cells treated with OGT/OGA inhibitor. Above findings suggested that OGT/OGA inhibitor regulated MUC4 protein level by affecting MUC4 O-GlcNAcylation to regulate ZO-1, GJB2, CLDN8, and E-cadherin protein levels in HConEpic cells, which was achieved via inhibiting the interaction between OGT/OGA and MUC4. This study may provide a better understanding of the pathogenesis of allergic conjunctivitis (AC).

Prevalence and molecular characterization of Clostridioides difficile infection in China over the past 5 years: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to provide an overview of the prevalence and molecular characteristics of Clostridioides difficile infection (CDI) in China in the past 5 years. METHODS: A systematic literature review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Nine databases were searched for relevant studies published between January 2017 and February 2022. The Joanna Briggs Institute critical appraisal tool was used to assess the quality of included studies, and R software version 4.1.3 was used for data analysis. Funnel plots and Egger regression tests were also performed to assess publication bias. RESULTS: A total of 50 studies were included in the analysis. The pooled prevalence of CDI in China was 11.4% (2696/26,852). The main circulating C. difficile strains in southern China were ST54, ST3, and ST37, consistent with the overall situation in China. However, the most prevalent genotype in northern China was ST2, which was previously underappreciated. CONCLUSION: Based on our findings, increased awareness and management of CDI is necessary to reduce the prevalence of CDI in China.

Mental health and psychosocial problems among laboratory technicians in response to the COVID-19 pandemic in Hebei, China.

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods: A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians' mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results: A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p < 0.001), more than 10 years of work experience (depression symptoms: OR = 2.350, p = 0.024; anxiety symptoms: OR = 2.642, p = 0.038), frontline work (depression symptoms: OR = 1.761, p = 0.001; anxiety symptoms: OR = 2.619, p < 0.001; hostility symptoms: OR = 1.913, p = 0.001), participant in more than 3 times large-scale SARS-CoV-2 screenings and more than 36 h per week in SARS-CoV-2 nucleic acid testing. Conclusion: A portion of laboratory technicians reported experiencing varying levels of psychological burden. During the COVID-19 pandemic, multiple interventions should be developed and implemented to address existing psychosocial challenges and promote the mental health of laboratory technicians.

Aerobic exercise regulates FGF21 and NLRP3 inflammasome-mediated pyroptosis and inhibits atherosclerosis in mice.

Fibroblast growth factor 21 (FGF21), a known risk factor for atherosclerosis, is readily regulated by exercise, and it can inhibit NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis. However, it is not clear whether aerobic exercise inhibits atherosclerosis via these pathways. Eight-week-old apolipoprotein E-deficient (ApoE-/-) mice on a high-fat diet were randomly divided into 1-h post-exercise (EX-1h), 24-h post-exercise (EX-24h), and sedentary (SED) groups. C57BL/6J wild-type mice fed normal chow served as controls (WT group). Mice in the EX-1h and EX-24h groups were subjected to treadmill exercise training for 12 weeks. Aerobic exercise reduced body weight; blood glucose, lipid, and inflammation levels; and aortic plaque area proportion. Aerobic exercise increased the sensitivity of FGF21 by upregulating the expression of the downstream receptor adiponectin (ApN); the serum FGF21 level after exercise increased initially, and then decreased. Aerobic exercise downregulated the expression of NLRP3 inflammasome-mediated pyroptosis-related markers in the aorta, and FGF21 may participate in the above process. Meanwhile, the liver may be the tissue source of serum FGF21 during aerobic exercise. In conclusion, aerobic exercise may inhibit atherogenesis by regulating FGF21 and NLRP3 inflammasome-mediated pyroptosis. Our study provides new information on the atherosclerosis-preventing mechanism of aerobic exercise.

The role of short-chain fatty acids in Clostridioides difficile infection: A review.

Clostridioides difficile is a Gram-positive, obligate anaerobic, spore-producing intestinal opportunistic pathogen. CDI outbreaks in Europe and the Americas in recent years are a major health concern. Intestinal short-chain fatty acids (SCFAs) are an important energy source for colonic epithelial cells, and the roles of SCFAs in reducing intestinal inflammation, inhibiting intestinal tumors, and regulating gut microbial homeostasis are being actively researched. Furthermore, SCFAs attenuate CDI or directly inhibit C. difficile growth through different pathways in vivo and in vitro. This review assesses the role of SCFAs in CDI and discusses the potential use of these molecules as therapeutic targets for CDI.

Treating Recurrent Brain Metastases Using GammaTile Brachytherapy: A Case Report and Dosimetric Modeling Method.

One of the treatment options for recurrent brain metastases is surgical resection combined with intracranial brachytherapy. GammaTile® (GT) (GT Medical Technologies, Tempe, Arizona) is a tile-shaped permanent brachytherapy device with cesium 131 (131Cs) seeds embedded within a collagen carrier. We report a case of treating a patient with recurrent brain metastases with GT and demonstrate a dosimetric modeling method.

Evaluation of Automated Treatment Planning and Organ Dose Prediction for Lung Stereotactic Body Radiotherapy.

PURPOSES: To evaluate whether the auto-planning (AP) module can achieve clinically acceptable treatment plans for lung stereotactic body radiotherapy (SBRT) and to evaluate the effectiveness of a dose prediction model. METHODS: Twenty lung SBRT cases planned manually with 50 Gy in five fractions were replanned using the Pinnacle (Philips Radiation Oncology Systems, Fitchburg, WI) AP module according to the dose constraint tables from the Radiation Therapy Oncology Group (RTOG) 0813 protocol. Doses to the organs at risk (OAR) were compared between the manual and AP plans. Using a dose prediction model from a commercial product, PlanIQ (Sun Nuclear Corporation, Melbourne, FL), we also compared OAR doses from AP plans with predicted doses. RESULTS: All manual and AP plans achieved clinically required dose coverage to the target volumes. The AP plans achieved equal or better OAR sparing when compared to the manual plans, most noticeable in the maximum doses of the spinal cord, ipsilateral brachial plexus, esophagus, and trachea. Predicted doses to the heart, esophagus, and trachea were highly correlated with the doses of these OARs from the AP plans with the highest correlation coefficient of 0.911, 0.823, and 0.803, respectively. CONCLUSION: Auto-planning for lung SBRT improved OAR sparing while keeping the same dose coverage to the tumor. The dose prediction model can provide useful planning dose guidance.

A Volumetric Dosimetry Analysis of Vertebral Body Fracture Risk After Single Fraction Spine Stereotactic Body Radiation Therapy.

PURPOSE: Vertebral compression fractures (VCF) are a common and severe complication of spine stereotactic body radiation therapy (SBRT). We sought to analyze how volumetric dosimetry and clinical factors were associated with the risk of VCF. METHODS AND MATERIALS: We evaluated 173 spinal segments that underwent single fraction SBRT in 85 patients from a retrospective database. Vertebral bodies were contoured and dosimetric values were calculated. Competing risk models were used to evaluate the effect of clinical and dosimetry variables on the risk of VCF. RESULTS: Our primary endpoint was development of a post-SBRT VCF. New or progressive fractures were noted in 21/173 vertebrae (12.1%); the median time to fracture was 322 days. Median follow-up time was 426 days. Upon multivariable analysis, the percentages of vertebral body volume receiving >20 Gy and >24 Gy were significantly associated with increased risk of VCF (hazard ratio, 1.036, 1.104; P = .029, .044, respectively). No other patient or treatment factors were found to be significant on multivariable analysis. Sensitivity analysis revealed that the percentages of vertebral body volume receiving >20 Gy and >24 Gy required to obtain 90% sensitivity for predicting vertebral body fracture were 24% and 0%, respectively. CONCLUSIONS: VCF is a common complication after SBRT, with a crude incidence of 12.1%. Treatment plans that permit higher volumes receiving doses >20 Gy and >24 Gy to the vertebral body are associated with increased risk of VCF. To achieve 90% sensitivity for predicting VCF post-SBRT, the percentage of vertebral volume receiving >20 Gy should be <24% and maximum point dose should be <24 Gy. These results may help guide clinicians when evaluating spine SBRT treatment plans to minimize the risk of developing posttreatment VCF.

[Study on secondary metabolites of endophytic fungus Cladosporium sp. JJM22 hosted in Ceriops tagal].

Nine secondary metabolites(S)-5-hydroxy-4-methylchroman-2-one(1), 4-methoxynaphthalene-1,5-diol(2), 8-methoxynaphthalene-1,7-diol(3), 1,8-dimethoxynaphthalene(4),(2R,4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol(5),(2R,4R)-3,4-dihydro-4-methoxy-2-methyl-2H-1-benzopyran-5-ol(6), 7-O-α-D-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one(7),(R)-3-methoxyl-1-(2,6-dihydroxyphenyl)-butan-1-one(8) and helicascolide A(9) were isolated from endophytic fungus Cladosporium sp. JJM22 by using column chromatographies of silica gel and ODS, and semi-preparative HPLC. Their structures were analyzed on the basis of spectroscopic and chemical data, especially NMR and MS. All isolated compounds were evaluated for their anti-inflammatory activities by examining the inhibitory activities on nitric oxide(NO) production induced by lipopolysaccharide in mouse macrophage RAW264.7 cells in vitro. Compounds 2-4 showed inhibitory activities.

Analysis of cardiac motion without respiratory motion for cardiac stereotactic body radiation therapy.

PURPOSE/OBJECTIVE(S): To study the heart motion using cardiac gated computed tomographies (CGCT) to provide guidance on treatment planning margins during cardiac stereotactic body radiation therapy (SBRT). MATERIALS/METHODS: Ten patients were selected for this study, who received CGCT scans that were acquired with intravenous contrast under a voluntary breath-hold using a dual source CT scanner. For each patient, CGCT images were reconstructed in multiple phases (10%-90%) of the cardiac cycle and the left ventricle (LV), right ventricle (RV), ascending aorta (AAo), ostia of the right coronary artery (O-RCA), left coronary artery (O-LCA), and left anterior descending artery (LAD) were contoured at each phase. For these contours, the centroid displacements from their corresponding average positions were measured at each phase in the superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP). The average volumes as well as the maximum to minimum ratios were analyzed for the LV and RV. RESULTS: For the six contoured substructures, more than 90% of the measured displacements were <5 mm. For these patients, the average volumes ranged from 191.25 to 429.51 cc for LV and from 91.76 to 286.88 cc for RV. For each patient, the ratios of maximum to minimum volumes within a cardiac cycle ranged from 1.15 to 1.54 for LV and from 1.34 to 1.84 for RV. CONCLUSION: Based on this study, cardiac motion is variable depending on the specific substructure of the heart but is mostly within 5 mm. Depending on the location (central or peripheral) of the treatment target and treatment purposes, the treatment planning margins for targets and risk volumes should be adjusted accordingly. In the future, we will further assess heart motion and its dosimetric impact.

Dosimetric assessment of patient-specific breath-hold reproducibility on liver motion for SBRT planning.

PURPOSE: To investigate the impact of breath-hold reproducibility on liver motion using a respiratory motion management device. METHODS: Forty-four patients with hepatic tumors, treated with SBRT with breath-hold, were randomly selected for this study. All patients underwent three consecutive computed tomography (CT) scans using active breath-hold coordinator (ABC) with three repeated single breath-hold during simulation. The three CT scans were labeled as ABC1-CT, ABC2-CT, and ABC3-CT. Displacements of centroids of the entire livers among the three ABC-CTs were measured as a surrogate for intrafractional motion. For each patient, two different treatment plans were prepared: (a) a clinical plan using a 5-mm expansion of an ITV that encompassed all three GTVs from each of the three ABC-CTs, and (b) a research plan using a 5-mm expansion of the GTV from only ABC1-CT to create PTV. The clinical plan acceptance criteria were that 95% of the PTV and 99% of the GTV received 100% of the prescription dose. Dosimetric endpoints were analyzed and compared for the two plans. RESULTS: All shifts in the medial-lateral direction (range: -3.9 to 2.0 mm) were within 5 mm while 7% of shifts in the anterior-posterior direction (range: -10.5 to 16.7 mm) and 11% of shifts in the superior-inferior direction (range: -17.0 to 8.7 mm) exceeded 5 mm. Six patients (14%) had an intrafraction motion greater than 5 mm in any direction. For these six patients, if a plan was created based on a PTV from a single CT (ex. ABC1-CT), 5 of 12 GTVs captured from other ABC-CTs would fail to meet the clinical acceptance criteria due to poor breath-hold reproducibility. CONCLUSIONS: Non-negligible intrafractional motion occurs in patients with poor breath-hold reproducibility. To identify this subgroup of patients, acquiring three CTs with active breath-hold during simulation is a feasible practical method.

Validation of RTOG 0813 Proximal Bronchial Tree Constraints for Pulmonary Toxicity With Stereotactic Body Radiation Therapy for Central Non-small Cell Lung Cancer.

PURPOSE: Clinical validation of protocol-specified dosimetric constraints for the proximal bronchial tree (PBT) is limited for central non-small cell lung cancer treated with stereotactic body radiation therapy. We sought to validate Radiation Therapy Oncology Group (RTOG) PBT constraints with a large institutional data set. METHODS AND MATERIALS: Lesions ≤2 cm from the PBT treated with definitive stereotactic body radiation therapy from 2009 to 2016 were identified from a prospective registry of 1462 patients. Every PBT dose and volume combination, ranging from 0 cGy to 8000 cGy in increments of 10 cGy and volumes ranging from 0.03 cm3 to 50 cm3 in increments of 0.03 cm3, was analyzed. The sensitivity and specificity of these endpoints for identifying pulmonary toxicity were calculated. Pulmonary toxicity was classified as pneumonitis or nonpneumonitis toxicity (NPT) (fistula, stenosis, necrosis, hemoptysis, clinically significant pleural effusion). The optimal dosimetric predictor was chosen by calculation of F-score (highest sensitivity and specificity). RESULTS: The study included 132 patients, with 26.0-month median follow-up. Eight grade ≥2 NPT (2 grade 5) and 8 grade 2 pneumonitis toxicities were observed. The PBT dosimetric endpoint with the highest F-score for identification of grade 2 to 5 NPT was D0.03cc ≤5000 cGy and that for grade 3 to 5 NPT was D0.33cc ≤4710 cGy, with sensitivity and specificity of 87.5% and 76.6% and 100.0% and 85.7%, respectively. Applying the RTOG 0813 PBT constraints to our data set achieved a sensitivity and specificity of 33.3% and 92.1% for D4cc ≤1800 cGy and 37.5% and 92.7% for D0.03cc ≤5250 cGy for identification of grade 2 to 5 NPT. A PBT dosimetric correlation for pneumonitis toxicity could not be identified. CONCLUSIONS: This novel dosimetric analysis validates current RTOG constraints and emphasizes high-dose, small-volume constraints as better predictors for NPT. We demonstrated that a slightly lower maximum point dose PBT constraint may be optimal for identification of NPT. Validation of these findings in a larger cohort of patients with longer follow-up is necessary.

Treatment planning of VMAT and step-and-shoot IMRT delivery techniques for single fraction spine SBRT: An intercomparative dosimetric analysis and phantom-based quality assurance measurements.

PURPOSE: To retrospectively compare clinically treated step-and-shoot intensity modulated radiotherapy (ssIMRT) and volumetric modulated arc therapy (VMAT) spine stereotactic body radiotherapy (SBRT) plans in dosimetric endpoints and pretreatment quality assurance (QA) measurements. METHODS: Five single fraction spine SBRT (18 Gy) cases - including one cervical, two thoracic, and two lumbar spines - clinically treated with ssIMRT were replanned with VMAT, and all plans were delivered to a phantom for comparing plan quality and delivery accuracy. Furthermore, we analyzed 98 clinically treated plans (18 Gy single fraction), including 34 ssIMRT and 29 VMAT for cervical/thoracic spine, and 19 ssIMRT and 16 VMAT for lumbar spine. The conformality index (CI) and homogeneity index (HI) were calculated, and QA measurement records were compared. For the spinal cord/cauda equina, the maximum dose to 0.03 cc (D0.03cc ) and volume receiving 10 or 12 Gy (V10Gy /V12Gy ) were recorded. Statistical significance was tested with the Mann-Whitney U test. RESULTS: Compared to ssIMRT, replanned VMAT plans had lower V10Gy /V12Gy and D0.03cc to the spinal cord/cauda equina in all five cases, and better CI in three out of five cases. The VMAT replans were slightly less homogeneous than those of ssIMRT plans. Both modalities passed IMRT QA with >95% passing rate with (3%, 3 mm) gamma criteria. With the 98 clinical cases, for cervical/thoracic ssIMRT and VMAT plans, the median V10Gy of spinal cord was 4.15% and 1.85% (P = 0.004); the median D0.03cc of spinal cord was 10.85 Gy and 10.10 Gy (P = 0.032); the median CI was 1.28 and 1.08 (P = 0.009); the median HI were 1.34 and 1.33 (P = 0.697), respectively. For lumbar spine, no significant dosimetric endpoint differences were observed. The two modalities were comparable in delivery accuracy. CONCLUSION: From our clinically treated plans, we found that VMAT plans provided better dosimetric quality and comparable delivery accuracy when compared to ssIMRT for single fraction spine SBRT.

Evaluation of auto-planning in IMRT and VMAT for head and neck cancer.

PURPOSE: The purposes of this work are to (a) investigate whether the use of auto-planning and multiple iterations improves quality of head and neck (HN) radiotherapy plans; (b) determine whether delivery methods such as step-and-shoot (SS) and volumetric modulated arc therapy (VMAT) impact plan quality; (c) report on the observations of plan quality predictions of a commercial feasibility tool. MATERIALS AND METHODS: Twenty HN cases were retrospectively selected from our clinical database for this study. The first ten plans were used to test setting up planning goals and other optimization parameters in the auto-planning module. Subsequently, the other ten plans were replanned with auto-planning using step-and-shoot (AP-SS) and VMAT (AP-VMAT) delivery methods. Dosimetric endpoints were compared between the clinical plans and the corresponding AP-SS and AP-VMAT plans. Finally, predicted dosimetric endpoints from a commercial program were assessed. RESULTS: All AP-SS and AP-VMAT plans met the clinical dose constraints. With auto-planning, the dose coverage of the low dose planning target volume (PTV) was improved while the dose coverage of the high dose PTV was maintained. Compared to the clinical plans, the doses to critical organs, such as the brainstem, parotid, larynx, esophagus, and oral cavity were significantly reduced in the AP-VMAT (P < 0.05); the AP-SS plans had similar homogeneity indices (HI) and conformality indices (CI) and the AP-VMAT plans had comparable HI and improved CI. Good agreement in dosimetric endpoints between predictions and AP-VMAT plans were observed in five of seven critical organs. CONCLUSION: With improved planning quality and efficiency, auto-planning module is an effective tool to enable planners to generate HN IMRT plans that are meeting institution specific planning protocols. DVH prediction is feasible in improving workflow and plan quality.

Evidence for Fast Lithium-Ion Diffusion and Charge-Transfer Reactions in Amorphous TiO x Nanotubes: Insights for High-Rate Electrochemical Energy Storage.

The charge-storage kinetics of amorphous TiO x nanotube electrodes formed by anodizing three-dimensional porous Ti scaffolds are reported. The resultant electrodes demonstrated not only superior storage capacities and rate capability to anatase TiO x nanotube electrodes but also improved areal capacities (324 µAh cm-2 at 50 µA cm-2 and 182 µAh cm-2 at 5 mA cm-2) and cycling stability (over 2000 cycles) over previously reported TiO x nanotube electrodes using planar current collectors. Amorphous TiO x exhibits very different electrochemical storage behavior from its anatase counterpart as the majority of its storage capacity can be attributed to capacitive-like processes with more than 74 and 95% relative contributions being attained at 0.05 and 1 mV s-1, respectively. The kinetic analysis revealed that the insertion/extraction process of Li+ in amorphous TiO x is significantly faster than in anatase structure and controlled by both solid-state diffusion and interfacial charge-transfer kinetics. It is concluded that the large capacitive contribution in amorphous TiO x originates from its highly defective and loosely packed structure and lack of long-range ordering, which facilitate not only a significantly faster Li+ diffusion process (diffusion coefficients of 2 × 10-14 to 3 × 10-13 cm2 s-1) but also more facile interfacial charge-transfer kinetics than anatase TiO x.

Low-Temperature Solution Processed Random Silver Nanowire as a Promising Replacement for Indium Tin Oxide.

A low-temperature solution-based process for depositing silver nanowire (AgNW) networks for use as transparent conductive top electrode is demonstrated. These AgNWs when applied to Cu2ZnSnS4 solar cells outperformed indium tin oxide as the top electrode. Thinner nanowires allow the use of lower temperatures during processing, while longer wires allow lowered sheet resistance for the same surface coverage of NWs, enhancing the transmittance/conductance trade-off. Conductive atomic force microscopy and percolation theory were used to study the quality of the NW network at the microscale. Our optimized network yielded a sheet resistance of 18 Ω/□ and ∼95% transmission across the entire wavelength range of interest for a deposition temperature as low as of 60 °C. Our results show that AgNWs can be used for low-temperature cell fabrication using cheap solution-based processes that could also be promising for other solar cells constrained to low processing temperatures such as organic and perovskite solar cells.

Following the Preclinical Data: Leveraging the Abscopal Effect More Efficaciously.

Radiotherapy is employed in the treatment of over 50% of cancer patients. However, this therapy approach is limited to mainly treating localized disease. In 1953, Mole described the remarkable abscopal effect, whereby, localized radiotherapy of a patient's primary tumor might engender regression of cancer at distant sites, which were not irradiated. Current consensus is that if the abscopal effect can be efficaciously leveraged, it would transform the field of radiation oncology, extending the use of radiotherapy to treatment of both localized and metastatic disease. A close examination of the literature on the abscopal effect proffers a disruptive new hypothesis for consideration in future clinical trials. This hypothesis is that generating a subcutaneous human tumor autograft as the primary tumor may be a more efficacious approach to prime the abscopal effect. Following the preclinical data, the merits and demerits of such an approach are examined in this article.

Nanoparticle-aided external beam radiotherapy leveraging the Cerenkov effect.

This study investigates the feasibility of exploiting the Cerenkov radiation (CR) present during external beam radiotherapy (EBRT) for significant therapeutic gain, using titanium dioxide (titania) nanoparticles (NPs) delivered via newly designed radiotherapy biomaterials. Using Monte Carlo radiation transport simulations, we calculated the total CR yield inside a tumor volume during EBRT compared to that of the radionuclides. We also considered a novel approach for intratumoral titania delivery using radiotherapy biomaterials (e.g. fiducials) loaded with NPs. The intratumoral distribution/diffusion of titania released from the fiducials was calculated. To confirm the CR induced enhancement in EBRT experimentally, we used 6MV radiation to irradiate human lung cancer cells with or without titania NPs and performed clonogenic assays. For a radiotherapy biomaterial loaded with 20µg/g of 2-nm titania NPs, at least 1µg/g could be delivered throughout a tumor sub-volume of 2-cm diameter after 14days. This concentration level could inflict substantial damage to cancer cells during EBRT. The Monte Carlo results showed the CR yield by 6MV radiation was higher than by the radionuclides of interest and hence greater damage might be obtained during EBRT. In vitro study showed significant enhancement with 6MV radiation and titania NPs. These preliminary findings demonstrate a potential new approach that can be used to take advantage of the CR present during megavoltage EBRT to boost damage to cancer cells. The results provide significant impetus for further experimental studies towards the development of nanoparticle-aided EBRT powered by the Cerenkov effect.

Potential of using cerium oxide nanoparticles for protecting healthy tissue during accelerated partial breast irradiation (APBI).

The purpose of this study is to investigate the feasibility of using cerium oxide nanoparticles (CONPs) as radical scavengers during accelerated partial breast irradiation (APBI) to protect normal tissue. We hypothesize that CONPs can be slowly released from the routinely used APBI balloon applicators-via a degradable coating-and protect the normal tissue on the border of the lumpectomy cavity over the duration of APBI. To assess the feasibility of this approach, we analytically calculated the initial concentration of CONPs required to protect normal breast tissue from reactive oxygen species (ROS) and the time required for the particles to diffuse to various distances from the lumpectomy wall. Given that cerium has a high atomic number, we took into account the possible inadvertent dose enhancement that could occur due to the photoelectric interactions with radiotherapy photons. To protect against a typical MammoSite treatment fraction of 3.4Gy, 5ng·g(-1) of CONPs is required to scavenge hydroxyl radicals and hydrogen peroxide. Using 2nm sized NPs, with an initial concentration of 1mg·g(-1), we found that 2-10days of diffusion is required to obtain desired concentrations of CONPs in regions 1-2cm away from the lumpectomy wall. The resultant dose enhancement factor (DEF) is less than 1.01 under such conditions. Our results predict that CONPs can be employed for radioprotection during APBI using a new design in which balloon applicators are coated with the NPs for sustained/controlled in-situ release from within the lumpectomy cavity.

Angular matrix framework for light trapping analysis of solar cells.

Complex light trapping structures make it challenging to simulate the optical properties of solar cells accurately. In this paper, a framework is proposed where matrices are used to describe the transition of the angular distribution of the light when it is reflected, transmitted or absorbed. The matrices can be computed using a range of different simulation methods and when parts of a complex structure are to be optimized, or the incident light is altered, the pre-computed matrices can be used with the potential benefit of saving computational time. The optical properties of silicon wafers with different texturing, surface coatings and light incident angles were simulated and compared with measurements to demonstrate the accuracy of the proposed framework. It is shown that different simulation methods can be effectively integrated to model different parts of the solar cell and structures with multiple coherent and incoherent layers. These features enable efficient and rapid evaluation of the optical properties of the device as a function of its physical properties.