Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Effect of concentration and wavelength of excitation on the photophysics of salicylate anion in acetonitrile and water.

Sodium salicylate (NaSA) molecule exists as salicylate anion in acetonitrile (ACN) and water solvents, and exhibits large Stokes shifted fluorescence due to excited state intramolecular proton transfer (ESIPT), with decay times of âˆ¼5 ns in ACN and âˆ¼3.9 ns in water by 300 nm (absorption maxima) excitation. Previous studies report both ground and excited state enol-keto tautomerization in ACN, but only excited state tautomerization in water at 10-4 M. However, the current work explores the effect of concentration and excitation wavelengths on the photoinduced dynamics of ESIPT in the salicylate anion. On increasing the concentration of NaSA, no change in absorption spectra appears in both the solvents, and emission spectra of NaSA in water remain unaffected by changes in concentration or excitation wavelength, whereas, a slight red shift and decrease in FWHM appears in ACN. Time-domain fluorescence measurements show predominantly single-exponential decay throughout the emission profile by 300 nm excitation above the 10-5 M concentration in both the solvents, while by 375 nm excitation, multi-exponential fluorescence decay is observed at low concentrations, and as the concentration of NaSA increases, this decay behaviour tends to converge towards a single exponential decay. These results suggest that solute-solvent interactions stabilize the ground-state intermolecular hydrogen-bonded species at low concentrations, while higher concentrations weaken these interactions, leading to emission solely from the salicylate anion. Peak fit analysis of excitation spectra confirms enol-keto tautomerization in both the solvents, with the keto form being more stabilized in ACN. These findings underscore that in ACN, behaviour of NaSA is influenced by both concentration and excitation wavelength and contrary to previous reports, the keto form of the molecule is also present in water, though at a very low concentration and an increase in non-radiative transitions in water cause fluorescence quenching.

Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy vs. IMRT for Localized Prostate Cancer.

PURPOSE/OBJECTIVES: Men with localized prostate cancer may receive either photon-based intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). The XXXXX trial (NCT01617161), demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT to PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials. MATERIALS/METHODS: Patients with low- or intermediate-risk prostate cancer were randomized to either PBT or IMRT with stratification by institution, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs. moderate hypofractionation: 70.0 Gy in 28 fractions). The primary endpoint is a change from baseline bowel health using the EPIC score 24 months after radiotherapy. Secondary objectives include treatment-related differences in urinary and erectile functions, adverse events, and efficacy endpoints. RESULTS: Between 07/2012 and 11/2021, 450 patients were successfully accrued. Patients were randomized to either PBT (N=226) or to IMRT (N=224); 13 were ineligible or withdrew prior to treatment. The median age of 437 analyzed patients was 68 years (range 46-89). 41% of patients had low-risk and 59% had intermediate-risk disease. 49% of patients were treated with conventional fractionation and 51% with moderately hypofractionation. For patients receiving PBT, 48% used a rectal balloon, 44% a rectal spacer, and 5% both. For patients receiving IMRT, 46% used a rectal balloon, 42% a rectal spacer, and 5% both. PBT and IMRT arms were balanced for baseline variables. CONCLUSIONS: Despite significant challenges, the XXXXX trial demonstrated that, with targeted recruitment approaches, multicenter collaboration, payer engagement, and protocol updates to incorporate contemporary techniques, it is feasible to perform a large phase III randomized clinical trial to assess whether PBT improves outcomes. We will separately report primary results and continue to monitor participants for longer followup and secondary endpoints.

Evaluation of lymphovascular space invasion in endometrial carcinoma by APTw and mDixon-Quant.

BACKGROUND: Lymphovascular space invasion (LVSI) is a strong and independent risk factor that increases the probability of endometrial carcinoma (EC) recurrence and reduces the survival rate of patients. PURPOSE: To investigate the value of amide proton transfer weighted (APTw) and mDixon-Quant techniques in evaluating EC lymphovascular space invasion (LVSI). MATERIAL AND METHODS: Data of 50 EC patients (18 LVSI+ and 32 LVSI-) confirmed by surgery and pathology were retrospectively analyzed. Preoperative magnetic resonance imaging (MRI) scans included APTw and mDixon-Quant imaging. APT, transverse relaxation rate (R2*), and fat fraction (FF) plots were obtained by postprocessing. The APT, R2*, and FF values of the two groups of cases were measured by two observers. RESULTS: The agreement between the two observers was good. The mean APT, R2*, and FF values of LVSI+ EC were 2.947% ± 0.399%, 20.605 /s (range = 18.525-27.953), and 2.234% ± 1.047%, respectively, while the parameters of LVSI- EC were 2.628% ± 0.307%, 18.968 /s (range = 16.225-20.544), and 2.103% ± 1.070%, respectively. The APT and R2* values of LVSI+ EC were higher than those of LVSI- EC (P < 0.05). There was no significant difference in FF value between the two groups. The AUC values of APT, R2*, and APT + R2* for LVSI were 0.751, 0.713, and 0.781, respectively (all P > 0.05). APT value was moderately correlated with R2* value (r = 0.528, P < 0.001) and weakly correlated with FF value (r = 0.312, P = 0.027). CONCLUSION: APTw and mDixon-Quant techniques could evaluate the LVSI status of EC, and their combined application could improve diagnostic efficiency.

Prevalence and resistance of Helicobacter pylori in a predominantly Hispanic population.

BACKGROUND: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in humans. The risk of acquiring H. pylori is related to socioeconomic status and living conditions early in life. Treatment regimens must consider local antibiotic resistance patterns. Adventist Health White Memorial Hospital serves a predominantly indigent population in east Los Angeles with a large number of immigrants from South and Central America. Data regarding the prevalence and resistance of H. pylori in this population is scant. AIM: To evaluate the prevalence and resistance of H. pylori and correlate with country of origin. METHODS: All gastric biopsies were obtained by a single gastroenterologist at the hospital in a consecutive manner from patients with gastritis from 2017 to 2022 and sent to various labs for evaluation. RESULTS: Two hundred and sixty-six patients are born in the United States, 450, 171, 70, and 30 patients are immigrants from Mexico, Central and South America (CSA), Asia, and other countries respectively. Overall, 14.65% were found to be infected with H. pylori. Rates of infection in United States-born citizens, immigrants from Mexico, CSA, and Asia are 9.02%, 18.67%, 13.45%, and 11.43% respectively, with Mexican immigrants having a relative risk of 2.3889 [95% confidence interval (CI): 1.4789-3.8588, P = 0.0004] compared to those born in United States. No correlation seen between infection and length of time immigrants were in United States. Relative risk of infection in patients with no proton pump inhibitor use within the past 30 days found to be 1.9276 (95%CI: 1.3562-2.7398, P = 0.0003). Rates of resistance for clarithromycin and levofloxacin are 21.43% and 31.11%. CONCLUSION: H. pylori infection appears to be associated with low socioeconomic status and poor living conditions early in life. Clarithromycin and levofloxacin based treatment regimens should be avoided as first line therapy in this region, particularly in patients of Latin American origin.

Topologically Close-Packed Frank-Kasper C15 Phase Intermetallic Ir Alloy Electrocatalysts Enables High-Performance Proton Exchange Membrane Water Electrolyzer.

Chemical synthesis of unconventional topologically close-packed intermetallic nanocrystals (NCs) remains a considerable challenge due to the limitation of large volume asymmetry between the components. Here, a series of unconventional intermetallic Frank-Kasper C15 phase Ir2M (M = rare earth metals La, Ce, Gd, Tb, Tm) NCs is successfully prepared via a molten-salt assisted reduction method as efficient electrocatalysts for hydrogen evolution reaction (HER). Compared to the disordered counterpart (A1-Ir2Ce), C15-Ir2Ce features higher Ir-Ce coordination number that leads to an electron-rich environment for Ir sites. The C15-Ir2Ce catalyst exhibits excellent and pH-universal HER activity and requires only 9, 16, and 27 mV overpotentials to attain 10 mA cm-2 in acidic, alkaline, and neutral electrolytes, respectively, representing one of the best HER electrocatalysts ever reported. In a proton exchange membrane water electrolyzer, the C15-Ir2Ce cathode achieves an industrial-scale current density of 1 A cm-2 with a remarkably low cell voltage of 1.7 V at 80 °C and can operate stably for 1000 h with a sluggish voltage decay rate of 50 µV h-1. Theoretical investigations reveal that the electron-rich Ir sites intensify the polarization of *H2O intermediate on C15-Ir2Ce, thus lowering the energy barrier of the water dissociation and facilitating the HER kinetics.

A Universal Strategy to Enhance Polarization Performance and Anode Reversal Tolerance by Polyaniline-Coated Carbon Support for Proton Exchange Membrane Fuel Cells.

Anode cell reversal typically leads to severe carbon corrosion and catalyst layer collapse, which significantly compromises the durability of proton exchange membrane fuel cells. Herein, three types of commercial carbon supports with various structures are facilely coated by polyaniline (PANI) and subsequently fabricated into reversal-tolerant anodes (RTAs). Consequently, the optimized PANI-coated catalyst RTAs demonstrate enhanced polarization performance and improved reversal tolerance compared to their uncoated counterparts, thus confirming the universality of this coating strategy. Essentially, the surface engineering introduced by PANI coating incorporates abundant N-groups and enhances coulombic interactions with ionomer side chains, which in turn reduces lower carbon exposure, promotes more uniform Pt deposition, and ensures better ionomer distribution. Accordingly, the membrane-electrode-assembly containing the Pt/PANI/XC-72R-1+IrO2 RTA presents a 100 mV (at 2500 mA cm-2) polarization performance improvement and 26-fold reduction in the degradation rate compared to the uncoated counterpart. This work provides a universal strategy for developing durable anodes and lays the groundwork for the practical fabrication of high-performance, low-degradation RTA.

Evaluation of a prototype array for daily quality assurance in spot scanning proton therapy.

BACKGROUND: Quality assurance (QA) on a daily basis is an essential task in radiotherapy. In pencil beam scanning proton therapy (PBS), there is a lack of available practical QA devices for routine daily QA in comparison to conventional radiotherapy. PURPOSE: The aim was to characterize and evaluate a prototype for the task of daily QA routine for PBS with parameters recommended by the AAPM TG 224, that is, the dose output constancy, the spot position and the distal range verification. Furthermore, a time efficient calibration method for fast and reliable daily QA routine was established for the prototype. METHODS: First, a calibration routine was designed and evaluated, which characterizes the array response and allows for a conversion of the measured signal to clinically needed QA parameters. Finally, a time and resource efficient daily QA routine was developed and tested. RESULTS: The prototype array can distinguish spot position deviations with sub-millimeter accuracy, as well as changes in the spot size in terms of FWHM with a 2 % $\%$ sensitivity. The range and thus the energy can be evaluated at different depths also with sub-millimeter precision. After some training, the setup of the prototype device took roughly two minutes and the total beamtime was about one minute on cyclotron site and five minutes for synchrotrons. CONCLUSIONS: A prototype for daily QA in spot scanning proton therapy was evaluated, which features a fast and easy setup and allows for measuring relevant beam parameters, typically within less than a minute of beam time. All QA parameters as recommended by the AAPM TG 224 report can be analyzed with sufficient accuracy.

Superior antitumor immune response achieved with proton over photon immunoradiotherapy is amplified by the nanoradioenhancer NBTXR3.

Recent findings suggest that immunoradiotherapy (IRT), combining photon radiotherapy (XRT) or proton radiotherapy (PRT) with immune checkpoint blockade, can enhance systemic tumor control. However, the comparative efficacy of XRT and PRT in IRT remains understudied. To address this, we compared outcomes between XRT + αPD1 and PRT + αPD1 in murine αPD1-resistant lung cancer (344SQR). We also assessed the impact of the nanoparticle radioenhancer NBTXR3 on both XRT + αPD1 and PRT + αPD1 for tumor control and examined the tumor immune microenvironment using single-cell RNA sequencing (scRNAseq). Additionally, mice cured by NBTXR3 + PRT + αPD1 were rechallenged with three lung cancer cell lines to evaluate memory antitumor immunity. PRT + αPD1 showed superior local tumor control and abscopal effects compared to XRT + αPD1. NBTXR3 + PRT + αPD1 significantly outperformed NBTXR3 + XRT + αPD1 in tumor control, promoting greater infiltration of antitumor lymphocytes into irradiated tumors. Unirradiated tumors treated with NBTXR3 + PRT + αPD1 had more NKT cells, CD4 T cells, and B cells, with fewer Tregs, than those treated with NBTXR3 + XRT + αPD1. NBTXR3 + PRT + αPD1 also stimulated higher expression of IFN-γ, GzmB, and Nkg7 in lymphocytes, reduced the TGF-ß pathway, and increased tumor necrosis factor alpha expression compared to NBTXR3 + XRT + αPD1. Moreover, NBTXR3 + PRT + αPD1 resulted in greater M1 macrophage polarization in both irradiated and unirradiated tumors. Mice achieving remission through NBTXR3 + PRT + αPD1 exhibited a robust memory immune response, effectively inhibiting growth of subsequent tumors from three distinct lung cancer cell lines. Proton IRT combined with NBTXR3 offers enhanced tumor control and survival rates over photon-based treatments in managing αPD1-resistant lung cancer, indicating its potential as a potent systemic therapy.

Proton Density Fat Fraction Quantification (PD-FFQ): Capability for hematopoietic ability assessment and aplastic anemaia diagnosis of adults.

PURPOSE: The purpose of this study was to determine the capability of proton density with fat fraction (PD-FFQ) imaging to help assess hematopoietic ability and diagnose aplastic anemia in adults. METHODS: Between January 2021 and March 2023, patients diagnosed with aplastic anemia (AA: n = 14) or myelodysplastic syndrome (MDS: n = 14) were examined by whole-body PD-FFQ imaging, and 14 of 126 age and gender matched patients who had undergone the same PD-FFQ imaging were selected as control group. All proton density fat fraction (PDFF) index evaluations were then performed by using regions of interest (ROIs). Pearson's correlation was used to determine the relationship between blood test results and each quantitative index, and ROC-based positive test and discrimination analyses to compare capability to differentiate the AA from the non-AA group. Finally, sensitivity, specificity and accuracy of all quantitative indexes were compared by means of McNemar's test. RESULTS: Mean PDFF, standard deviation (SD) and percentage of coefficient of variation (%CV) for vertebrae showed significant correlation with blood test results (-0.52 ≤ r ≤ -0.34, p < 0.05). Specificity (SP) and accuracy (AC) of %CV of PDFF in vertebrae were significantly higher than those of mean PDFF in vertebrae and the posterior superior iliac spine (SP: p = 0.0002, AC: p = 0.0001) and SD of PDFF in vertebrae (SP: p = 0.008, AC: p = 0.008). Moreover, AC of SD of PDFF in vertebrae was significantly higher than that of mean PDFF in vertebrae and the posterior superior iliac spine (p = 0.03). CONCLUSION: Whole-body PD-FFQ imaging is useful for hematopoietic ability assessment and diagnosis of aplastic anemia in adults.

First test beam of the DMAPS-based proton tracker at the pMBRT facility at the Curie Institute.

\textbf{Objective.} Proton radiotherapy's efficacy relies on an accurate Relative Stopping Power (RSP) map of the patient to optimise the treatment plan and minimize uncertainties. Currently, a conversion of a Hounsfield Units (HU) map obtained by a common X-ray Computed Tomography (CT) is used to compute the RSP. This conversion is one of the main limiting factors for proton radiotherapy. To bypass this conversion a direct RSP map could be obtained by performing a proton CT (pCT). The focal point of this article is to present a proof of concept of the potential of fast pixel technologies for proton tracking at clinical facilities. \textbf{Approach.} A two-layer tracker based on the TJ-Monopix1, a Depleted Monolithic Active Pixel Sensor (DMAPS) chip initially designed for the ATLAS, was tested at the proton MiniBeam RadioTherapy (pMBRT) beamline at the Curie Institute. The chips were subjected to 100 MeV protons passing through the single slit collimator (0.4$\times$20 mm$^2$) with fluxes up to $1.3 \times 10^7$ p/s/cm$^2$. The performance of the proton tracker was evaluated with GEANT4 simulations. \textbf{Main Results:} The beam profile and dispersion in air were characterized by an opening of 0.031~mm/cm, and a $\sigma_x=0.172$~mm at the position of the slit. The results of the proton tracking show how the TJ-Monopix1 chip can effectively track protons in a clinical environment, achieving a tracking purity close to~70~$\%$, and a position resolution below 0.5 mm; confirming the chip's ability to handle high proton fluxes with a competitive performance. \textbf{Significance:} This work suggests that DMAPS technologies can be a cost-effective alternative for proton imaging. Additionally, the study identifies areas where further optimization of chip design is required to fully leverage these technologies for clinical ion imaging applications.

Investigation of interfractional range variation owing to anatomical changes with beam directions based on water equivalent thickness in proton therapy for pancreatic cancer.

To assess the interfractional anatomical range variations (ARVs) with beam directions and their impact on dose distribution in intensity modulated proton therapy, we analyzed water equivalent thickness (WET) from 10 patients with pancreatic cancer. The distributions of the interfractional WET difference ($\Delta{\mathrm{WET}}^{\theta }$) across 360° were visualized using polar histograms. Interfractional ARVs were evaluated using the mean absolute error and ΔWET pass rate, indicating the percentage of $\Delta \mathrm{WE}{\mathrm{T}}^{\theta }$ < thresholds. The impact on dose distribution in proton therapy was evaluated based on two treatment plans for 40 Gy(RBE)/5 fractions: 'Plan A', using two beam angles, in which the target was closest to the body surface among four perpendicular directions; and 'Plan B', using two beam angles with small ARVs. Analysis revealed individual variations in angular trends of interfractional ARVs. Three distinct trends were identified: Group 1 exhibited small ARVs around posterior directions; Group 2 exhibited small ARVs except ~60°; Group 3 demonstrated minimal ARVs only ~90°. In dose evaluation, while 150° and 210° were selected in Plan B for 9 out of 10 patients, for the remaining patient, 60° and 90° were chosen. Comparing dose volume histogram parameters for all patients, Plan B significantly reduced target coverage loss while maintaining organ-at-risk sparing comparable to Plan A. These results demonstrated that selecting beam angles with small interfractional ARVs for each patient enhances the robustness of dose distribution, reducing target coverage loss.

Boosting Acidic Hydrogen Evolution Kinetics Induced by Weak Strain Effect in PdPt Alloy for Proton Exchange Membrane Water Electrolyzers.

Strain engineering is an effective strategy for manipulating the electronic structure of active sites and altering the binding strength toward adsorbates during the hydrogen evolution reaction (HER). However, the effects of weak and strong strain engineering on the HER catalytic activity have not been fully explored. Herein, the core-shell PdPt alloys with two-layer Pt shells (PdPt2L) and multi-layer Pt shells (PdPtML) is constructed, which exhibit distinct lattice strains. Notably, PdPt2L with weak strain effect just requires a low overpotential of 18 mV to reach 10 mA cm-2 for the HER and shows the superior long-term stability for 510 h with negligible activity degradation in 0.5 M H2SO4. The intrinsic activity of PdPt2L is 6.2 and 24.5 times higher than that of PdPtML and commercial Pt/C, respectively. Furthermore, PdPt2L||IrO2 exhibits superior activity over Pt/C||IrO2 in proton exchange membrane water electrolyzers and maintains stable operation for 100 h at large current density of 500 mA cm-2. In situ/operando measurements verify that PdPt2L exhibits lower apparent activation energy and accelerated ad-/desorption kinetics, benefiting from the weak strain effect. Density functional theory calculations also reveal that PdPt2L displays weaker H* adsorption energy compared to PdPtML, favoring for H* desorption and promoting H2 generation.

Proton beam therapy in a patient with secondary glioblastoma (32 years after postoperative irradiation of medulloblastoma): case report and literature review.

OBJECTIVE: This report details the experience of a patient who developed a second primary glioblastoma (GB), offering insights into the treatment process and reviewing relevant literature. CASE PRESENTATION: A male patient, who was diagnosed with medulloblastoma at age 9, received treatment with cobalt-60 craniospinal irradiation (CSI) (36 Gy/20 fractions) and a tumor bed boost (total of 56 Gy). After 32 years, at age 41, an MRI revealed a space-occupying mass in the left cerebellar hemisphere. Surgical resection was performed, and postoperative pathology confirmed a diagnosis of radiation-induced glioblastoma (RIGB). Given the history of irradiation and the current tolerability of brainstem doses, proton beam therapy (PBT) combined with Temozolomide (75 mg/m2) was chosen. The treatment plan included 60 Gy on the gross tumor bed and 54 Gy on the clinical target volume, delivered in 30 fractions. The patient underwent regular follow-up and achieved a complete response. CLINICAL DISCUSSION: For childhood cancer survivors, the development of a second primary tumor significantly impacts prognosis. RIGB is a rare form of secondary tumor with distinct molecular characteristics compared to primary GB and recurrent secondary GB. Molecular markers such as IDH and MGMT status can help differentiate between primary GB, recurrent secondary GB, and radiation-induced secondary GB in patients with a history of prior radiation therapy. Surgical resection remains a primary treatment option, while PBT is preferred for postoperative treatment due to its superior protection of normal tissues and the ability to deliver high-dose irradiation. CONCLUSION: RIGB is a rare second primary tumor that requires strategic molecular profiling and individualized management. Proton beam therapy provides effective high-dose irradiation in the postoperative phase and is the preferred treatment option for such cases.

Improving the feasibility of deprescribing proton pump inhibitors: GPs' insights on barriers, facilitators, and strategies.

Introduction: The prevalent overprescribing of proton pump inhibitors (PPIs) poses health risks from prolonged use. GPs play a key role in initiating deprescribing PPIs, so understanding their decision-making factors and strategies to improve feasibility is crucial. This study aimed to investigate the perspectives of GPs on deprescribing PPIs with a focus on identifying facilitators, barriers, and strategies to enhance feasibility in clinical settings. Methods: A qualitative study involving semi-structured interviews was conducted with nine GPs or trainees. The thematic analysis of the interviews was conducted using NVivo R1 (2020). Results: Four main categories were identified: 1) Inappropriate prescribing of PPIs, 2) Facilitators for deprescribing PPIs, 3) Barriers to deprescribing PPIs, 4) Feasibility of deprescribing PPIs. GPs acknowledged excessive and often inappropriate PPI prescribing, with a lack of deprescribing efforts mainly due to time constraints. Other key barriers included patient reluctance, fear of symptom recurrence, and unawareness of long-term risks. Patient-initiated request is key facilitator for deprescribing PPIs. GPs emphasized the need for collaboration with healthcare professionals, clear guidelines, improved digital support, increased physician availability, and raising awareness among providers and patients to enhance deprescribing feasibility. Discussion: GPs are calling for a multifaceted approach to improve the feasibility of deprescribing PPIs, involving patient-centered approaches, systemic optimizations, support from other healthcare professionals, and provider-centered strategies to emphasize the importance of deprescribing PPIs.

Sectored single-energy volumetric-modulated proton arc therapy (VPAT): A preliminary multi-disease-site concept study.

PURPOSE: To explore the feasibility of a novel intensity-modulated proton arc technique that uses a single-energy beam from the cyclotron. The beam energy is externally modulated at each gantry angle by a tertiary energy modulator (EM). We hypothesize that irradiating in an arc without requiring an energy change from the cyclotron will achieve a faster delivery (main advantage of our technique) while keeping clinically desirable dosimetric results. METHODS: In a retrospective cohort of four patients with female pelvis, prostate, lung, and brain cancers, we investigated our volumetric-modulated proton arc therapy (VPAT) technique. Arcs were simulated by sectors of 1°-spaced static beams. Keeping the energy requested from the cyclotron the same for each entire arc was supported by a predesigned EM placed in front of the nozzle. As a feasibility measure, EM thicknesses were calculated. Delivery times and doses to targets and organs at risk (OARs) were compared to those of the clinical plans. RESULTS: VPAT plans were comparable to their clinical counterparts in achieving target dose conformity, being robust to uncertainties, and meeting clinical dose-volume constraints. Cyclotron energies for the four cases were within 159-220 MeV, and energy modulation range was 69-100 MeV, equivalent to 13-19 cm of water-equivalent thickness (WET). Plan delivery times were reduced from > 5 min in our clinical practice to < 3.5 min in VPAT. CONCLUSION: For the evaluated plans, the novel VPAT approach achieved shorter delivery times without sacrificing robustness, OAR sparing or target coverage. VPAT's EMs had WETs implementable in a clinical setup.

A simulation study of MR-guided proton therapy system using iron-yoked superconducting open MRI: a conceptual study.

Radiotherapy platforms integrated with magnetic resonance imaging (MRI) have been significantly successful and widely used in X-ray therapy over the previous decade. MRI provides greater soft-tissue contrast than conventional X-ray techniques, which enables more precise radiotherapy with on-couch adaptive treatment planning and direct tracking of moving tumors. The integration of MRI into a proton beam irradiation system (PBS) is still in the research stage. However, this could be beneficial as proton therapy is more sensitive to anatomical changes and organ motion. In this simulation study, we considered the integration of PBS into the 0.3-T superconducting open MRI system. Our proposed design involves proton beams traversing a hole at the center of the iron yoke, which allows for a reduced fringe field in the irradiation nozzle while maintaining a large proton scan field of the current PBS. The shape of the bipolar MRI magnets was derived to achieve a large MRI field-of-view. To monitor the beam position and size accurately while maintaining a small beam size, the beam monitor installation was redesigned from the current system. The feasibility of this system was then demonstrated by the treatment plan quality, which showed that the magnetic field did not deteriorate the plan quality from that without the magnetic field for both a rectangular target and a prostate case. Although numerous challenges remain before the proposed simulation model can be implemented in a clinical setting, the presented conceptual design could assist in the initial design for the realization of the MR-guided proton therapy.

Fundamental and Practical Aspects of Break-In/Conditioning of Proton Exchange Membrane Fuel Cells.

Proton exchange membrane fuel cells (PEMFCs) have proven to be a promising power source for various applications ranging from portable devices to automotive and stationary power systems. The production of PEMFC involves numerous stages in the value chain, with each stage presenting unique challenges and opportunities to improve the overall performance and durability of the PEMFC stack. These include steps such as manufacturing the key components such as the platinum-based catalyst, processing these components into the membrane electrode assemblies (MEAs), and stacking the MEAs to ultimately produce a PEMFC stack. However, it is also known that the break-in or conditioning phase of the stack plays a crucial role in the final performance as well as durability. It involves several key phenomena such as hydration of the membrane, swelling of the ionomer, redistribution of the catalyst and the creation of suitable electrochemical interfaces - establishment of the triple phase boundary. These improve the proton conductivity, the mass transport of reactants and products, the catalytic activity of the electrode and thus the overall efficiency of the FC. The cruciality of break-in is demonstrated by the improvement in performance, which can even be over 50 % compared to the initial state. The state-of-the-art approach for the break-in of MEAs involves an electrochemical protocol, such as voltage cycling, using a PEMFC testing station. This method is time-consuming, equipment-intensive, and costly. Therefore, new, elegant, and cost-effective solutions are needed. Nevertheless, the primary aim is to achieve maximum/optimal performance so that it is fully operational and ready for the market. It is therefore essential to better understand and deconvolute these complex mechanisms taking place during break-in/conditioning. Strategies include controlled humidity and temperature cycling, novel electrode materials and other advanced break-in methods such as air braking, vacuum activation or steaming. In addition, it is critical to address the challenges associated with standardisation and quantification of protocols to enable interlaboratory comparisons to further advance the field.

Autodelineation methods in a simulated fully automated proton therapy workflow for esophageal cancer.

Background and purpose: Proton Online Adaptive RadioTherapy (ProtOnART) harnesses the dosimetric advantage of protons and immediately acts upon anatomical changes. Here, we simulate the clinical application of delineation and planning within a ProtOnART-workflow for esophageal cancer. We aim to identify the most appropriate technique for autodelineation and evaluate full automation by replanning on autodelineated contours. Materials and methods: We evaluated 15 patients who started treatment between 11-2022 and 01-2024, undergoing baseline and three repeat computed tomography (CT) scans in treatment position. Quantitative and qualitative evaluations compared different autodelineation methods. For Organs-at-risk (OAR) deep learning segmentation (DLS), rigid and deformable propagation from baseline to repeat CT-scans were considered. For the clinical target volume (CTV), rigid and three deformable propagation methods (default, heart as controlling structure and with focus region) were evaluated. Adaptive treatment plans with 7 mm (ATP7mm) and 3 mm (ATP3mm) setup robustness were generated using best-performing autodelineated contours. Clinical acceptance of ATPs was evaluated using goals encompassing ground-truth CTV-coverage and OAR-dose. Results: Deformation was preferred for autodelineation of heart, lungs and spinal cord. DLS was preferred for all other OARs. For CTV, deformation with focus region was the preferred method although the difference with other deformation methods was small. Nominal ATPs passed evaluation goals for 87 % of ATP7mm and 67 % of ATP3mm. This dropped to respectively 2 % and 29 % after robust evaluation. Insufficient CTV-coverage was the main reason for ATP-rejection. Conclusion: Autodelineation aids a ProtOnART-workflow for esophageal cancer. Currently available tools regularly require manual annotations to generate clinically acceptable ATPs.

A High-capacity Benzoquinone Derivative Anode for All-organic Long-cycle Aqueous Proton Batteries.

Quinone compounds, with the ability to uptake protons, are promising electrodes for aqueous batteries. However, their application is limited by the mediocre working potential range and inferior rate performance. Herein, we examined quinones bearing different substituents, and for the first time introduce tetraamino-1,4-benzoquinone (TABQ) as anode material for proton batteries. The strong electron-donating amino groups can effectively narrow the band gap and negatively shift the redox potentials of quinone material. The protonation of amino groups and the amorphization of structure result in the formation of an intermolecular hydrogen-bond network, supporting Grotthuss-type proton conduction in the electrode with a low activation energy of 192.7 meV. The energy storage mechanism revealed by operando FT-IR and ex-situ XPS features a reversible quinone-hydroquinone conversion during cycling. TABQ demonstrates a remarkable specific capacity of 307 mAh g-1 at 1 A g-1, which is the highest among organic proton electrodes. An all-organic proton battery of TABQ//TCBQ has also been developed, achieving exceptional stability of 3500 cycles at room temperature and excellent performance at sub-zero temperatures.