Search Results (884)

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Background and Clinical Significance: Sarcina ventriculi is a rare Gram-positive coccus that thrives in acidic environments such as the human stomach. It has been increasingly identified in individuals with delayed gastric emptying and has been reported in association with various gastric disorders. However, its exact pathogenic role is not fully understood and remains controversial. Case Presentation: We present two cases of patients, one with a small bowel obstruction and the other with epigastric pain, both diagnosed with Sarcina ventriculi infection by histological examination of gastric biopsies. The patients were managed with a combination of antibiotics and a proton pump inhibitor, resulting in symptom resolution and clearance of Sarcina ventriculi upon follow-up examinations. Conclusions: This report explores the pathogenicity of Sarcina ventriculi by documenting its presence in symptomatic patients without other identifiable pathogens and demonstrating complete symptom resolution following targeted therapy. These findings raise the possibility of Sarcina ventriculi’s pathogenic potential under specific clinical conditions, suggesting it may act as more than a benign colonizer. Full article

Hypomagnesemia is a frequent and often underrecognized electrolyte disturbance with important clinical consequences, especially in hospitalized and critically ill patients. This multifactorial condition arises from impaired intestinal absorption, renal magnesium wasting, and the effects of various medications. Magnesium, the second most abundant intracellular cation, is crucial in enzymatic and physiological processes; its deficiency is associated with neuromuscular, cardiovascular, and metabolic complications. This narrative review focuses on the mechanisms and clinical consequences of drug-induced hypomagnesemia, highlighting the major drug classes involved such as diuretics, antibiotics, antineoplastic agents, and immunosuppressants. Management strategies include magnesium supplementation and adjunctive therapies like amiloride and SGLT2 inhibitors to reduce renal magnesium losses. Recognizing and addressing drug-induced hypomagnesemia is essential to improve patient outcomes and prevent long-term complications. Full article

Proton therapy has emerged as a highly precise and tissue-sparing radiotherapy technique, capitalizing on the unique energy deposition pattern of protons characterized by the Bragg peak. Ensuring treatment accuracy relies on calibration phantoms, often composed of tissue-equivalent polymeric materials. This study investigates the dosimetric behavior of four commonly used polymers—Parylene, Epoxy, Lexan, and Mylar—by analyzing their linear energy transfer (LET) values and Bragg curve characteristics across various proton energies. Experimental LET data were collected and used to train and evaluate the predictive power for Bragg peak of multiple artificial intelligence models, including kNN, SVR, MLP, RF, LWRF, XGBoost, 1D-CNN, LSTM, and BiLSTM. These algorithms were optimized using 10-fold cross-validation and assessed through statistical error and performance metrics including MAE, RAE, RMSE, RRSE, CC, and R². Results demonstrate that certain AI models, particularly RF and LWRF, accurately (in terms of all evaluation metrics) predict Bragg peaks in Epoxy polymers, reducing the reliance on costly and time-consuming simulations. In terms of CC and R² metrics, the LWRF model demonstrated superior performance, achieving scores of 0.9969 and 0.9938, respectively. However, when evaluated against MAE, RMSE, RAE, and RRSE metrics, the RF model emerged as the top performer, yielding values of 12.3161, 15.8223, 10.3536, and 11.4389, in the same order. Additionally, the SVR model achieved the highest number of statistically significant differences when compared pairwise with the other eight models, showing significance against six of them. The findings support the use of AI as a robust tool for designing reliable calibration phantoms and optimizing proton therapy planning. This integrative approach enhances the synergy between materials science, medical physics, and data-driven modeling in advanced radiotherapy systems. Full article

Background/Objectives: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by the replacement of healthy bone marrow (BM) with malignant and fibrotic tissue. In a healthy state, bone marrow is composed of approximately 60–70% fat cells, which are replaced as disease progresses. Proton density fat fraction (PDFF), a non-invasive and quantitative MRI metric, enables analysis of BM architecture by measuring the percentage of fat versus cells in the environment. Our objective is to investigate variance in quantitative PDFF-MRI values over time as a marker of disease progression and response to treatment. Methods: We analyzed existing data from three cohorts of mice: two groups with MF that failed to respond to therapy with approved drugs for MF (ruxolitinib, fedratinib), investigational compounds (navitoclax, balixafortide), or vehicle and monitored over time by MRI; the third group consisted of healthy controls imaged at a single time point. Using in-house MATLAB programs, we performed a voxel-wise analysis of PDFF values in lower extremity bone marrow, specifically comparing the variance of each voxel within and among mice. Results: Our findings revealed a significant difference in PDFF values between healthy and diseased BM. With progressive disease non-responsive to therapy, the expansion of hematopoietic cells in BM nearly completely replaced normal fat, as determined by a markedly reduced PDFF and notable reduction in the variance in PDFF values in bone marrow over time. Conclusions: This study validated our hypothesis that the variance in PDFF in BM decreases with disease progression, indicating pathologic expansion of hematopoietic cells. We can conclude that disease progression can be tracked by a decrease in PDFF values. Analyzing variance in PDFF may improve the assessment of disease progression in pre-clinical models and ultimately patients with MF. Full article

Background/Objectives: Within the range of spread-out Bragg peak (SOBP), LET (linear energy transfer) gradually increases from proton beam entrance point toward the beam exit direction. While it is expected that the change in LET would lead to correspondent change in RBE (relative biological effectiveness) on many human cell lines, the incomplete cell killing due to low LET can result in tumor recurrence. Hence, this study aimed to assess the RBE on different cancer cell lines along low-LET proton SOBP. Methods: The clonogenicity of A549 and Panc-1 cells after irradiation was evaluated for investigating cell radiosensitivity in response to different types of radiation. The isoeffect doses of 6-MV photon and low-LET proton beams that resulted in equivalent cell surviving fractions at proton dose of 2 or 4 Gy were compared. Results: Ratios of α/β of A549 and Panc-1 cells from photon irradiation are 51.69 and −0.7747, respectively; RBE (2 Gy proton SOBP) on A549 and Panc-1 cells are 0.7403 ± 0.3324 and 1.0986 ± 0.3984, respectively. In addition, the change in RBE with proton LET was in a cell-specific and dose-dependent manner (LET-RBE linear correlations: A549 cells [r = 0.4673, p = 0.2430] vs. Panc-1 cells at 4 Gy [r = 0.7085, p = 0.0492]; Panc-1 cells at 2 Gy [r = −0.4123, p = 0.3100] vs. 4 Gy [r = 0.7085, p = 0.0492]). Conclusions: Compared with A549 cells, Panc-1 cells present greater resistance to low-LET proton beams. In addition, currently employed generic RBE value at 1.1 for proton therapy neglected the variation in cell-/tumor-specific radiobiological responses toward different dose levels of proton beams. Full article

Oligometastasis represents a clinically relevant state of limited metastatic disease that could be amenable to selected local therapies in carefully chosen patients. Although initial trials such as SABR-COMET demonstrated a survival benefit with aggressive local treatment, breast cancer was underrepresented. Subsequent breast cancer-specific trials, including NRG-BR002, failed to show a clear survival benefit, highlighting uncertainties and the need for further refinement in patient selection and integration with systemic approaches. The definitions of oligometastasis continue to evolve, incorporating radiological, clinical, and biological features. Advances in imaging and molecular profiling suggest that oligometastatic breast cancer might represent a distinct biological subtype, with potential biomarkers including PIK3CA mutations and YAP/TAZ expression. Organ-specific strategies using stereotactic radiotherapy, surgery, and proton therapy have shown favorable local control in certain settings, though their impact on the overall survival remains under investigation. Emerging techniques, including circulating tumor DNA (ctDNA) analysis, are being explored to improve patient selection and disease monitoring. Ongoing trials may provide further insight into the role of local therapy, particularly in hormone receptor-positive or HER2-positive subtypes. Local and systemic strategies need to be carefully coordinated to optimize the outcomes. This review summarizes the current definitions of and evidence and therapeutic considerations for oligometastatic breast cancer and outlines potential future directions. Full article

Social anxiety disorder (SAD) is characterized by fear and avoidance of social situations. Considering the reduced availability of conventional therapies, we aimed to improve our understanding of the biological mechanisms in SAD by evaluating gamma-aminobutyric acid (GABA) and other neurometabolites (including glutamate + glutamine/glutamix (Glx), N-acetyl aspartate (NAA), myo-inositol (mI), total choline (tCho), and total creatine (tCr) in the dorsomedial prefrontal cortex/anterior cingulate cortex (dmPFC/ACC), dorsolateral prefrontal cortex (dlPFC), and the insula). In this pilot study, we recruited 26 (age: 25.3 ± 5.0 years; 61.5% female) individuals with SAD and 26 (age: 25.1 ± 4.4 years; 61.5% female) sex-age-matched controls. Using proton magnetic resonance spectroscopy, we found that compared to the controls, GABA+ macromolecular signal (GABA+) in dlPFC (t = 2.63; p = 0.012) and Glx in the insula (Mann–Whitney U = 178.3; p = 0.024) were higher in the participants with SAD. However, no between-group differences were observed in dmPFC/ACC (t = 0.39; p = 0.699). Increased GABA+ in dlPFC could be explained by aberrant GABA transporters. In the insula, increased Glx may be associated with the dysfunction of glutamate transporters or decreased activity of glutamic acid decarboxylase in the GABAergic inhibitory neurons. However, these proposed mechanisms need to be further investigated in SAD. Full article

Background/Objectives: Proton therapy delivers highly conformal doses to the target area without producing an exit dose, minimizing cumulative doses to healthy liver tissue. This study aims to evaluate current practices, challenges, and variations in the implementation of proton stereotactic body radiation therapy (SBRT) and hypofractionated therapy for liver malignancies, with the goal of providing a technical assessment to promote broader adoption and support future clinical trials. Methods and Materials: An extensive survey was conducted by NRG Oncology across North American proton treatment centers to assess the current practices of proton liver SBRT and hypofractionated therapy. The survey focused on key aspects, including patient selection, prescription and normal tissue constraints, simulation and motion management, treatment planning, quality assurance (QA), treatment delivery, and the use of image-guided radiation therapy (IGRT). Results: This survey captures the current practice patterns and status of proton SBRT and hypofractionated therapy in liver cancer treatment.  Proton therapy is increasingly preferred for treating inoperable liver malignancies due to its ability to minimize healthy tissue exposure. However, the precision required for proton therapy presents challenges, particularly in managing uncertainties and target motion during high-dose fractions and short treatment courses. Survey findings revealed significant variability in clinical practices across centers, highlighting differences in motion management, dose fractionation schedules, and QA protocols. Conclusion: Proton SBRT and hypofractionated therapy offer significant potential for treating liver malignancies. A comprehensive approach involving precise patient selection, treatment planning, and QA is essential for ensuring safety and effectiveness. This survey provides valuable insights into current practices and challenges, offering a foundation for technical recommendations to optimize the use of proton therapy and guide future clinical trials. Full article

Proton pump inhibitors (PPIs) are widely prescribed medications primarily used to treat gastroesophageal reflux disease, peptic ulcer disease, and upper gastrointestinal bleeding. Despite clear therapeutic benefits in appropriate contexts, widespread overprescribing and extended use without clear indications have prompted significant concerns about associated risks. Accumulating evidence, predominantly from observational studies, suggests that long-term PPI use may lead to complications such as vitamin and mineral deficiencies, increased risks of infections, dysbiosis, renal dysfunction, bone fractures, cardiovascular disease, and certain malignancies. This narrative review not only synthesizes the current evidence surrounding PPI-related harms and existing deprescribing guidelines but also offers a novel perspective on how stewardship principles can be applied to promote responsible PPI prescribing. In particular, we propose a stewardship-oriented deprescribing framework rooted in implementation science, focusing on provider behavior, patient engagement, and health system-level integration. Recognizing these potential harms, evidence-based deprescribing strategies such as tapering, intermittent dosing, and transitions to alternative therapies are critical to mitigate unnecessary patient exposure. Effective implementation of deprescribing requires addressing patient, provider, and institutional barriers through educational initiatives, policy support, and structured monitoring. By promoting judicious PPI prescribing and proactive stewardship practices, clinicians can significantly reduce medication-related harm and improve patient safety. Full article

In this study, we describe the preparation of carbon dots (CDs) from natural charcoal by laser ablation in a liquid. A continuum wave (CW) laser diode operating at a wavelength of 450 nm, hitting a solid carbon target placed into a biocompatible liquid, constituted of a phosphate-buffered saline (PBS) solution and distilled water, was used for the generation of the CDs suspension. Exploring the practical applications of carbon dots, it was observed that the luminescence of the produced CDs can be used as bioimaging in living organisms, environmental monitoring, chemical analysis, targeted drug delivery, disease diagnosis, therapy, and others. The CDs’ luminescence can be induced by UV irradiation and, as demonstrated in this study, by energetic MeV proton beams. The fluorescence was revealed mainly at 480 nm when UV illuminated the CDs, and also in the region at 514–642 nm when the CDs were irradiated by energetic proton ions. Atomic force microscopy (AFM) of the CD films revealed their spherical shape with a size of about 10 nm. The significance of the manuscript lies in the use of CDs produced by laser ablation exhibiting luminescence under irradiation of an energetic proton beam. Full article

The main objective of proton beam therapy is to precisely irradiate diseased tissue while minimizing damage to healthy cells. For effective treatment, the linear energy transfer (LET) is a key parameter in ensuring the destruction of diseased cells, and both the dose and LET are typically represented as functions of depth. The distribution of dose and LET in the target depends on the beam properties, including beam energy, energy spread, beam size, and beam emittance. The aim of this work is to present the method used to characterize the proton beam properties obtained from the machine employed in the simulation and to determine the dose and dose-averaged LET (LET_d) values, including their peak positions in depth. These results are used to predict the dose and LET_d at different depth positions under experimental conditions. We utilized GEANT4, a Monte Carlo (MC) simulation-based software, to examine the integral depth-dose position and the peak position of the LET_d. The proton source was obtained from a cyclotron accelerator, specifically the Varian ProBeam Compact spot scanning system at King Chulalongkorn Memorial Hospital in Bangkok, Thailand. The system provides proton energies ranging from 70 MeV to 220 MeV. In this study, four proton energies—70 MeV, 100 MeV, 150 MeV, and 220 MeV—were chosen to characterize the beam properties. The 80%–20% distal fall-off obtained from the simulation was used to determine the energy spread for each selected energy by matching the depth-dose peak with the measurement data. The optimal energy spreads were found to be 1.5%, 1.25%, 1%, and 0.5% for proton energies of 70 MeV, 100 MeV, 150 MeV, and 220 MeV, respectively. These energy spreads ensure that the difference in the depth-dose profile is below 1% when comparing the simulated and measured depth-dose profiles. Furthermore, the peak LET_d was found to be approximately 1 mm away from the R₈₀ position, a depth that corresponds to 80% of maximum dose, for each energy. This information can be used to guide the desired LET_d position by utilizing the R₈₀ depth position. Full article

Background/Objectives: Inflammatory bowel disease (IBD) patients face elevated gastrointestinal (GI) infection risks due to immune dysregulation and gut dysbiosis. While steroids and immunosuppressants are known to increase infection risk, data on biologics and proton pump inhibitors (PPIs) remain limited, particularly for non-Clostridioides difficile (C.diff) infections. Methods: This retrospective cohort study analyzed 9849 hospitalized IBD patients (2013–2023) from the Northwell Inpatient Database. Patients were categorized into four groups: biologics-only, PPIs-only, both, or neither. GI infections were identified via C.diff PCR, GI PCR, and chart review. Multivariate logistic regression adjusted for demographics, BMI, and IBD type. Results: GI infections occurred in 1.75% of patients, with significantly higher odds in those on biologics alone (OR 21.5, 95% CI 11.7–39.4) or with PPIs (OR 16.6, 95% CI 10.2–26.8) versus untreated patients. Non-C.diff infections were strongly associated with biologics (OR 20.7, 95% CI 10.2–41.9). PPIs alone increased slightly the risk of GI infections (OR 1.6, 95% CI 1.1–2.4). Vedolizumab and adalimumab had the highest infection risks among biologics (26.8% and 22.7%, respectively). Bacterial pathogens, such as E. coli and Salmonella, predominated, with no significant difference in causative agents across treatment groups. Conclusions: Biologic therapy greatly increases GI infection risk in IBD patients independent of PPI use. Clinicians should weigh infection risks when prescribing biologics, particularly in high-risk populations. Further studies are needed to assess risks by biologic subtype and the interplay with PPIs. Full article

This work presents the experimental results of a wavelet transform denoising algorithm (WTDA) that improves the ionoacoustic signal-to-noise ratio (SNR) and proton range measurement precision. Ionoacoustic detectors exploit the ultrasound signal generated by pulsed proton beams in energy absorbers (water or the human body) to localize the energy deposition with sub-millimeter precision, with interesting applications in beam monitoring during oncological hadron therapy treatments. By improving SNR and measurement precision, the WTDA allows significant reduction of the extra dose necessary for beam characterization. To validate the WTDA’s performance, two scenarios are presented. First, the WTDA was applied to the ionoacoustic signals from a 20 MeV proton beam, where it allowed for increasing the SNR by 17 dB and improving measurement precision by a factor of two. Then, the WTDA was applied to the simulated signals from a 200 MeV clinical beam where, compared to state-of-the-art algorithms, it achieved a −80% dose reduction when achieving the same 30 μm precision and a six-fold precision improvement for the same 17 Gy dose deposition. Full article

Background: Up to one-third of patients with gastroesophageal reflux disease (GERD) have persistent symptoms despite proton-pump inhibitor (PPI) therapy. E-Gastryal^® + MgAlg (Aurora Biofarma, Italy) is a mucosal protective agent that enhances barrier function against acid and non-acidic reflux. This study assessed its efficacy in combination with omeprazole versus omeprazole alone and as maintenance therapy. Methods: Patients with symptomatic GERD and Grade A reflux esophagitis confirmed by endoscopy were randomized to receive omeprazole 20 mg plus E-Gastryal^® + MgAlg or omeprazole 20 mg alone. The primary endpoint was the number of rescue medications used over 28 days. Secondary endpoints included symptom relief and quality-of-life assessments using the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Impact Scale (GIS), GERD-Health-Related Quality of Life (GERD-HRQL), and Global Assessment of Performance (IGAP). Results: Ninety-six patients were included. The combination group used significantly fewer rescue medications (mean: 21 vs. 40.9 tablets; p = 0.002). At week 4, the combination group showed greater improvement in RSI, GIS, and GERD-HRQL scores (p < 0.001). Symptom relief was sustained during weeks 5–26 with E-Gastryal^® + MgAlg alone. Conclusions: E-Gastryal^® + MgAlg combined with omeprazole improves symptom control compared to PPI monotherapy. Continued use as maintenance therapy supports its role in long-term GERD management (NCT04130659). Full article