\u3ci\u3eAcrobasis\u3c/i\u3e Shoot Moth (Lepidoptera: Pyralidae) Infestation-Tree Height Link in a Young Black Walnut Plantation

Acrobasis shoot moth infestations were evaluated in a young black walnut progeny test for 4 years, from ages 3 to 6. Infestation levels were greatest on the largest trees in the fourth and fifth year after plantation establishment, and were declining by the sixth year. Acrobasis infestation appears to be a problem primarily on young trees less than 2.5 m in height. There was no evidence for genetic resistance to Acrobasis infestation in black walnut

Design and in vivo characterization of self-inactivating human and non-human lentiviral expression vectors engineered for streptogramin-adjustable transgene expression

Adjustable transgene expression is considered key for next-generation molecular interventions in gene therapy scenarios, therapeutic reprogramming of clinical cell phenotypes for tissue engineering and sophisticated gene-function analyses in the post-genomic era. We have designed a portfolio of latest generation self-inactivating human (HIV-derived) and non-human (EIAV-based) lentiviral expression vectors engineered for streptogramin-adjustable expression of reporter (AmySΔS, EYFP, SAMY, SEAP), differentiation-modulating (human C/EBP-α) and therapeutic (human VEGF) transgenes in a variety of rodent (CHO-K1, C2C12) and human cell lines (HT-1080, K-562), human and mouse primary cells (NHDF, PBMC, CD4+) as well as chicken embryos. Lentiviral design concepts include (i) binary systems harboring constitutive streptogramin-dependent transactivator (PIT) and PIT-responsive transgene expression units on separate lentivectors; (ii) streptogramin-responsive promoters (PPIR8) placed 5′ of desired transgenes; (iii) within modified enhancer-free 3′-long terminal repeats; and (iv) bidirectional autoregulated configurations providing streptogramin-responsive transgene expression in a lentiviral one-vector format. Rigorous quantitative analysis revealed HIV-based direct PPIR-transgene configurations to provide optimal regulation performance for (i) adjustable expression of intracellular and secreted product proteins, (ii) regulated differential differentiation of muscle precursor cell lines into adipocytes or osteoblasts and (iii) conditional vascularization fine-tuning in chicken embryos. Similar performance could be achieved by engineering streptogramin-responsive transgene expression into an autoregulated one-vector format. Powerful transduction systems equipped with adjustable transcription modulation options are expected to greatly advance sophisticated molecular interventions in clinically and/or biotechnologically relevant primary cells and cell line

Clinical Outcome After Pencil Beam Scanning Proton Therapy of Patients With Non-Metastatic Malignant and Benign Peripheral Nerve Sheath Tumors.

Objective Peripheral nerve sheath tumors (PNSTs) commonly arise from peripheral nerve roots and grow locally invasive. Malignant PNSTs (mPNSTs) represent aggressive sarcomas of neural origin that can originate from PNSTs. Radiation therapy is commonly used as part of the required multimodal treatment. However, both entities tend to occur early in life and are associated with the genetic disorder neurofibromatosis type 1 (NF-1), which is known to cause increased radiosensitivity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of the dose delivered to organs at risk and the integral dose and, thus, potentially also a reduction of radiation-induced adverse events. We report the clinical outcome and toxicity rates of patients with (m)PNSTs treated with PBSPT. Methods We retrospectively reviewed 36 patients who received PBSPT (median dose, 64 GyRBE) with curative intent for (m)PNSTs between 1999 and 2020 at our institute. Twenty-eight (78%) and 8 (22%) patients were treated at diagnosis and for tumor recurrence/progression, respectively. The median age was 32 years (range, 3-75), and 25 (69%) patients were male. mPNST and PNST were diagnosed in 31 (86%) and 5 (14%) patients, respectively. Underlying NF-1 disease was found in 8 (22%) patients. Acute and late toxicities were recorded according to Common Terminology Criteria for Adverse Events, version 4.1 (CTCAE v4.1). Overall survival (OS), local control (LC), and distant control (DC) were estimated using the Kaplan-Meier method. Results With a median follow-up time of 31 months (range, 4-194), 13 (36%) patients died from a progressive disease, 8 (22%) experienced local failure, and 14 (39%) experienced distant failure after PBSPT. Estimated 2-year OS, LC, and DC were 75.5%, 73.5%, and 61.2%, respectively. Acute grade 3 toxicity (dermatitis, mucositis, and pain) was observed in 5 (14%) patients. Late grade 3 cataract and osteonecrosis were both observed in 1 (3%) patient at 34 and 194 months after PBSPT, respectively. There was no late grade >3 toxicity or radiation-induced secondary cancer. Conclusion To our knowledge, this is the first study to analyze the outcome of (m)PNSTs treated with proton therapy using a PBS delivery paradigm. In our cohort, consisting mainly of patients with mPNSTs, we report reasonable oncological outcomes and low toxicity rates after PBSPT

Financial Toxicity in Swiss Cancer Patients Treated with Proton Therapy: An Observational Cross-Sectional Study on Self-Reported Outcome

BACKGROUND Proton therapy is indicated for cancers that would be difficult to treat with conventional radiotherapy. Compulsory healthcare insurance covers the costs of this therapy in Switzerland, but this does not mean that proton therapy is cost-neutral for every cancer patient. Significant out-of-pocket (OOP) costs may arise due to expenses associated with proton therapy, and patients may experience treatment-related financial distress-an effect known as "financial toxicity." This study investigates the financial toxicity of patients undergoing proton therapy in a high-income country with a compulsory health insurance policy. METHODS Between September 2019 and November 2021, 146 Swiss cancer patients treated with proton therapy participated in this study, of whom 90 (62%) were adults and 56 (38%) were caregivers of child cancer patients. Financial toxicity was assessed using the FACIT Comprehensive Score for Financial Toxicity (COST). OOP costs during proton therapy were recorded weekly, and financial coping strategies were captured at the end of treatment. FINDINGS The median COST score, indicating financial toxicity, was 29.9 (IQR 21.0; 36.0) for all patients, 30.0 (IQR 21.3; 37.9) for adults, and 28.0 (IQR 20.5; 34.0) for children's caregivers. Higher income (estimate 8.1, 95% CI 3.7 to 12.4, p ≤ 0.001) was significantly associated with higher COST scores, indicating less financial toxicity. Further distance from home to the treatment centre per 100 km (estimate -3.7, 95% CI -5.7 to -1.9, p ≤ 0.001) was significantly associated with lower COST scores, indicating increased financial toxicity. Married adult patients had substantially lower COST scores than single patients (estimate: -9.1, 95% CI -14.8 to -3.4, p ≤ 0.001). The median OOP cost was 2050 Swiss francs (CHF) and was spent mainly on travel, accommodation, and eating out. Sixty-three (43%) patients used their savings; 54 (37%) cut spending on leisure activities; 21 (14.4%) cut living expenses; 14 (9.6%) borrowed money; nine (6.2%) worked more; and four (2.7%) sold property. Patients with high COST scores used significantly fewer coping strategies such as saving on leisure activities (estimate -9.5, 95% CI -12.4 to -6.6, p ≤ 0.001), spending savings (estimate -3.9, 95% CI -6.3 to -1.4, p = 0.002), borrowing money (estimate -6.3, 95% CI -10.4 to -2.2, p = 0.003), and increasing workload (estimate -5.5, 95% CI -10.5 to -0.4, p = 0.035). INTERPRETATION A substantial number of cancer patients treated with proton therapy experience financial toxicity in Switzerland. Long travel distances to the proton therapy centre and low income negatively affect the financial well-being of these patients during proton therapy

Treatment planning comparison for head and neck cancer between photon, proton, and combined proton-photon therapy - From a fixed beam line to an arc

BACKGROUND AND PURPOSE: This study investigates whether combined proton-photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. MATERIAL AND METHODS: Five HNC patients with a planning CT and multiple (4-7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. RESULTS: The target coverage for CPPT without adaptation is insufficient (average V95%=88.4 %), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5 %) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are -2.7 %/-3.4 %/-5.0 % for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are + 0.8 %/-0.9 %/-4.3 %. CONCLUSION: CPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined

Treatment planning comparison for head and neck cancer between photon, proton, and combined proton-photon therapy - from a fixed beam line to an arc.

BACKGROUND AND PURPOSE This study investigates whether combined proton-photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. MATERIAL AND METHODS Five HNC patients with a planning CT and multiple (4-7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. RESULTS The target coverage for CPPT without adaptation is insufficient (average V95%=88.4%), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5%) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are -2.7%/-3.4%/-5.0% for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are +0.8%/-0.9%/-4.3%. CONCLUSION CPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined

Threshold Dose for Shrimp: A Risk Characterization Based on Objective Reactions in Clinical Studies

A DBPCFC [double-blind, placebo-controlled food challenge] of shrimp-allergic adults was conducted to obtain individual threshold doses. Results of this study and published research were combined and a population threshold for shrimp was determined from dose-distribution modeling. The shrimp-allergic population seems to have a higher threshold compared to other populations for other food allergens. Additional shrimp challenges should be done to confirm these initial results

Finite Element Simulation Combination to Predict the Distortion of Thin Walled Milled Aluminum Workpieces as a Result of Machining Induced Residual Stresses

Machining induced residual stresses (MIRS) are a main driver for distortion of monolithic thin walled aluminum workpieces. A typical machining process for manufacturing such geometries for the aerospace industry is milling. In order to avoid high costs due to remanufacturing or part rejection, a simulation combination, consisting of two different finite element method (FEM) models, is developed to predict the part distortion due to MIRS. First, a 3D FEM cutting simulation is developed to predict the residual stresses due to machining. This simulation avoids cost intensive residual stress measurements. The milling process of the aluminum alloy AA7050-T7451 with a regular end mill is simulated. The simulation output, MIRS, forces and temperatures, is validated by face milling experiments on aluminum. The model takes mechanical dynamic effects, thermomechanical coupling, material properties and a damage law into account. Second, a subsequent finite element simulation, characterized by a static, linear elastic model, where the simulated MIRS from the cutting model are used as an input and the distortion of the workpiece is calculated, is presented. The predicted distortion is compared to an additional experiment, where a 1 mm thick wafer was removed at the milled surface of the aluminum workpiece. Furthermore, a thin walled component that represents a down scaled version of an aerospace component is manufactured and its distortion is analyzed. The results show that MIRS could be forecasted with moderate accuracy, which leads to the conclusion that the FEM cutting model needs to be improved in order to use the MIRS for a correct prediction of the distortion with the help of the linear elastic FEM model. The linear elastic model on the other hand is able to predict the part distortion with higher accuracy when using measured data instead of MIRS from the cutting simulation

A Unified Generation-Registration Framework for Improved MR-based CT Synthesis in Proton Therapy

Background: In MR-guided proton therapy planning, aligning MR and CT images is key for MR-based CT synthesis, especially in mobile regions like the head-and-neck. Misalignments here can lead to less accurate synthetic CT (sCT) images, impacting treatment precision. Purpose: This study introduces a novel network that cohesively unifies image generation and registration processes to enhance the quality and anatomical fidelity of sCTs derived from better-aligned MR images. Methods: The approach synergizes a generation network (G) with a deformable registration network (R), optimizing them jointly in MR-to-CT synthesis. This goal is achieved by alternately minimizing the discrepancies between the generated/registered CT images and their corresponding reference CT counterparts. The generation network employs a UNet architecture, while the registration network leverages an implicit neural representation of the Deformable Vector Fields (DVFs). We validated this method on a dataset comprising 60 Head-and-Neck patients, reserving 12 cases for holdout testing. Results: Compared to the baseline Pix2Pix method with MAE 124.95\pm 30.74 HU, the proposed technique demonstrated 80.98\pm 7.55 HU. The unified translation-registration network produced sharper and more anatomically congruent outputs, showing superior efficacy in converting MR images to sCTs. Additionally, from a dosimetric perspective, the plan recalculated on the resulting sCTs resulted in a remarkably reduced discrepancy to the reference proton plans. Conclusions: This study conclusively demonstrates that a holistic MR-based CT synthesis approach, integrating both image-to-image translation and deformable registration, significantly improves the precision and quality of sCT generation, particularly for the challenging body area with varied anatomic changes between corresponding MR and CT

Hearing Loss in Cancer Patients with Skull Base Tumors Undergoing Pencil Beam Scanning Proton Therapy: A Retrospective Cohort Study.

To assess the incidence and severity of changes in hearing threshold in patients undergoing high-dose pencil-beam-scanning proton therapy (PBS-PT). This retrospective cohort study included fifty-one patients (median 50 years (range, 13-68)) treated with PBS-PT for skull base tumors. No chemotherapy was delivered. Pure tone averages (PTAs)were determined before (baseline) and after PBS-PT as the average hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz. Hearing changes were calculated as PTA differences between pre-and post-PBS-PT. A linear mixed-effects model was used to assess the relationship between the PTA at the follow-up and the baseline, the cochlea radiation dose intensity, the increased age, and the years after PBS-PT. Included patients were treated for chordoma (n = 24), chondrosarcoma (n = 9), head and neck tumors (n = 9), or meningioma (n = 3), with a mean tumor dose of 71.1 Gy (RBE) (range, 52.0-77.8), and a mean dose of 37 Gy (RBE) (range, 0.0-72.7) was delivered to the cochleas. The median time to the first follow-up was 11 months (IQR, 5.5-33.7). The PTA increased from a median of 15 dB (IQR 10.0-25) at the baseline to 23.8 (IQR 11.3-46.3) at the first follow-up. In the linear mixed-effect model, the baseline PTA (estimate 0.80, 95%CI 0.64 to 0.96, p ≤ 0.001), patient's age (0.30, 0.03 to 0.57, p = 0.029), follow-up time (2.07, 0.92 to 3.23, p ≤ 0.001), and mean cochlear dose in Gy (RBE) (0.34, 0.21 to 0.46, p ≤ 0.001) were all significantly associated with an increase in PTA at follow-up. The applied cochlear dose and baseline PTA, age, and time after treatment were significantly associated with hearing loss after proton therapy