UNASSIGNED: Repeated cone-beam CT (CBCT) scans for image-guided radiotherapy (IGRT) increase the health risk of radiation-induced malignancies. Patient-enrolled studies to optimize scan protocols are inadequate. We proposed a virtual clinical trial-based approach to evaluate projection-reduced low-dose CBCT for IGRT.
UNASSIGNED: A total of 71 patients were virtually enrolled with 26 head, 23 thorax and 22 pelvis scans. Projection numbers of full-dose CBCT scans were reduced to 1/2, 1/4, and 1/8 of the original to simulate low-dose scans. Contrast-to-noise ratio (CNR) values in fat and muscle were measured in the full-dose and low-dose images. CBCT images were registered to planning CT to derive 6-degree-of-freedom couch shifts. Registration errors were statistically analyzed with the Wilcoxon paired signed-rank test.
UNASSIGNED: As projection numbers were reduced, CNR values descended and the magnitude of registration errors increased. The mean CNR values of full-dose and half-dose CBCT were >3.0. For full-dose and low-dose CBCT (i.e. 1/2, 1/4 and 1/8 full-dose), the mean registration errors were< ± 0.4 mm in translational directions (LAT, LNG, VRT) and ±0.2 degree in rotational directions (Pitch, Roll, Yaw); the mean magnitude of registration errors were< 1 mm in translation and< 0.5 degree in rotation. The couch shift differences between full-dose and low-dose CBCT were not statistically significant (p>0.05) in all the directions.
UNASSIGNED: The results indicate that while the impact of dose-reduction on CBCT couch shifts is not significant, the impact on CNR values is significant. Further validation on optimizing CBCT imaging dose is required.

UNASSIGNED: Osimertinib is more efficacious and as safe as first-generation epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors. However, osimertinib is not affordable for most patients in developing nations. Moreover, the minimum biologically effective dose of osimertinib may be less than the approved dose.
UNASSIGNED: This was a retrospective observational multicentric study aimed to describe the efficacy (objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS)) and toxicity of osimertinib 80 mg orally administered less frequently than daily (ranging from every other day to once-a-week) in patients with EGFR-mutated non-small cell lung cancer.
UNASSIGNED: Between January 2021 and August 2023, we enrolled 22 patients. Six received osimertinib 80 mg once-a-week, nine received 80 mg once-in-3-days and seven received 80 mg on alternate days. Responses included 0 complete responses, 7 (31.8%) partial responses, 9 (40.9%) stable disease and 5 (22.7%) progressive disease. ORR was 31.8%, and DCR was 72.7%. Median PFS was 9.2 months (95% confidence interval (CI) 2.9-15.7), and median OS was 17.8 months (95% CI, 3.2-32.6). In patients who received reduced frequency osimertinib in the second line and beyond, the ORR was 29.4%, DCR was 70.5%, median PFS was 5.9 months (95% CI, 1.1-10.6) and median OS was 17.6 months (95% CI, 2.9-32.2). Grade 3 and higher toxicities were noted in 8 (36.3%) patients.
UNASSIGNED: Less frequent dosing of osimertinib may be a valid treatment option, especially in the second line and beyond setting in patients who cannot afford full dose daily osimertinib. This may provide an additional treatment option with a similar toxicity profile as that of standard dose osimertinib.

The Planning and Acting Network for Low Dose Radiation Research in Japan (PLANET) was established in 2017 in response to the need for an all-Japan network of experts. It serves as an academic platform to propose strategies and facilitate collaboration to improve quantitative estimation of health risks from ionizing radiation at low-doses and low-dose-rates. PLANET established Working Group 1 (Dose-Rate Effects in Animal Experiments) to consolidate findings from animal experiments on dose-rate effects in carcinogenesis. Considering international trends in this field as well as the situation in Japan, PLANET updated its priority research areas for Japanese low-dose radiation research in 2023 to include (i) characterization of low-dose and low-dose-rate radiation risk, (ii) factors to be considered for individualization of radiation risk, (iii) biological mechanisms of low-dose and low-dose-rate radiation effects and (iv) integration of epidemiology and biology. In this context, PLANET established Working Group 2 (Dose and Dose-Rate Mapping for Radiation Risk Studies) to identify the range of doses and dose rates at which observable effects on different endpoints have been reported; Working Group 3 (Species- and Organ-Specific Dose-Rate Effects) to consider the relevance of stem cell dynamics in radiation carcinogenesis of different species and organs; and Working Group 4 (Research Mapping for Radiation-Related Carcinogenesis) to sort out relevant studies, including those on non-mutagenic effects, and to identify priority research areas. These PLANET activities will be used to improve the risk assessment and to contribute to the revision of the next main recommendations of the International Commission on Radiological Protection.

In 1992, the Committee on Neurotoxicology and Models for Assessing Risk of the National Academy of Sciences in Washington DC focused with a scientific perspective on the identification of substances with neurotoxic potential, studies of exposed populations, risk assessment, and biologic markers of disease. This Committee recommended: \"all physicians should be trained to take a thorough occupational-exposure history and to be aware of other possible sources of toxic exposure\". Although convened after several outbreaks of neurotoxic syndromes, clinical neurological considerations were lacking. After defining keys words, namely Environment, Neurotoxicology and Neurotoxicants, we present some demonstrative cases; e.g., the Epidemic Neuropathy in Cuba, Minamata disease, ALS/PDC on Guam, and the ALS hot spot in the French Alps. Always with a clinical and practical approach, we will then review the milieux that contain and convey potential neurotoxicants, the different exposure routes and the clinical presentations. Drawing lessons from clinical cases, we offer some thoughts concerning the future of Environmental Neurotoxicology (ENT). Pointing notably to the diffuse chemical contamination of ecosystems and living beings, including Homo sapiens, we question the real impact of agents with neurotoxic potential on the human brain, considering the effects, for example, of air pollution, endocrine disruptors and nanoparticles. Concern is expressed over the lack of knowledge of the non-monotonic kinetics of many of these chemicals, the major concern being related to mixtures and low-dose exposures, as well as the delayed appearance in clinical expression of prevalent neurodegenerative diseases.

UNASSIGNED: To evaluate the performance of calcium quantification on photon-counting detector CT (PCD-CT) with high-pitch at low radiation doses compared to third-generation dual-source energy-integrating detector CT (EID-CT).
UNASSIGNED: The phantom with three calcium inserts (50, 100, and 300 mg of calcium per milliliter), with and without the elliptical outer layer, was evaluated using high-pitch (3.2) and standard pitch (0.8) on PCD-CT, and standard pitch on EID-CT. Scans were performed with different tube voltages (PCD-CT: 120 and 140 kilo-voltage peak [kVp]; EID-CT: 70/Sn150 and 100/Sn150 kVp) and four radiation doses (1, 3, 5, and, 10 milli-Gray [mGy]). Utilizing the true calcium concentrations (CCtrue) of the phantom as the gold standard references, regression equations for each kVp setting were formulated to convert CT attenuations (CaCT) into measured calcium concentrations (CCm). The correlation analysis between CaCT and CCtrue was performed. The percentage absolute bias (PAB) was calculated from the differences between CCm and CCtrue and used to analyze the effects of scanning parameters on calcium quantification accuracy.
UNASSIGNED: A strong correlation was found between CaCT and CCtrue on PCD-CT (r > 0.99) and EID-CT (r > 0.98). For high- and standard-pitch scans on PCD-CT, the accuracy of calcium quantification is comparable (p = 0.615): the median (interquartile range [IQR]) of PAB was 5.59% (2.79%-8.31%) and 4.87 % (2.62%-8.01%), respectively. The PAB median (IQR) was 7.43% (3.77%-11.75%) for EID-CT. The calcium quantification accuracy of PCD-CT is superior to EID-CT at the large phantom (5.46% [2.68%-9.55%] versus 9.01% [6.22%-12.74%]), and at the radiation dose of 1 mGy (4.43% [2.08%-8.59%] versus 13.89% [8.93%-23.09%]) and 3 mGy (4.61% [2.75%-6.51%] versus 9.97% [5.17%-14.41%]), all p < 0.001.
UNASSIGNED: Calcium quantification using low-dose PCD-CT with high-pitch scanning is feasible and accurate, and superior to EID-CT.

OBJECTIVE: This study aims to develop Various Age-size Pediatric Chest Phantoms (VAPC) to evaluate low-dose protocol that approximates clinical conditions achieved by low organ-specific doses and optimal image quality among the challenges of pediatric size variations.
METHODS: Three original pediatric data aged 1, 4, and 7 years were used as a reference for developing VAPC phantoms. Six protocols, namely standard dose (STD) and low dose (low mA and low kV) reconstructed using Filtered Back Projection (FBP) and iterative reconstruction (IR) algorithms, were investigated. This study directly measured the lungs, heart, and spinal cord dose using LD-V1 film. Linearity, Modulation Transfer Function (MTF), Contrast to Noise Ratio (CNR), and Noise Power Spectrum (NPS) were evaluated to assess the CT image quality of the VAPC phantom.
RESULTS: This study found that the mean organ-specific dose was higher than CTDIvol. A Comparison of mean lung doses showed VAPC phantom 1 (y.o.) received 74.8% and 137.2% more doses than 4 (y.o.) and 7 (y.o.), respectively. Low kV produces a lower organ dose than low mA. The linearity of CT numbers is not biased at low doses. Differences in age measures significantly influenced organ-specific dose, MTF, CNR, and NPS.
CONCLUSIONS: Smaller pediatrics are still exposed to higher doses at low-dose examinations, whereas larger pediatrics have lower contrast resolution and increased image noise. CT number linearity is unbiased. The combination of low kV with FBP produces higher spatial resolution, while low mA with IR effectively reduces noise to detect low-contrast objects better.

The effects of tritium at low doses and low dose rates have received increasing attention due to recent developments in fusion energy and the associated risks of tritium releases into the environment. Mitochondria have been identified as a potential candidate for studying the effects of low-dose/low-dose-rate radiation, with extensive experimental results obtained using X-ray irradiation. In this study, irradiation experiments were conducted on normal B-lymphoblastoid cells using HTO at varying doses. When compared to X-ray irradiation, no significant differences in cell viability induced by different doses were observed. However, the results of ATP levels showed a significant difference between the irradiated sample at a dose of 500 mGy by tritium beta-rays and the sham-irradiated sample, while the levels obtained with X-ray irradiation were almost identical to the sham-irradiated sample. In contrast, ATP levels for both tritium beta-rays and X-rays at a dose of 1.0 Gy showed minimal differences compared to the sham-irradiated sample. Furthermore, distinct effects at 500 mGy were also confirmed in both ROS levels and apoptosis results obtained through tritium beta-ray irradiation. This suggests that mitochondria might be a potential sensitive target for investigating the effects of tritium beta-ray irradiation.

UNASSIGNED: The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission.
UNASSIGNED: This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML.
UNASSIGNED: This was a retrospective study.
UNASSIGNED: Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction.
UNASSIGNED: This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8-98.7) and 90.5% (95% CI: 81.3-95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction (p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients.
UNASSIGNED: Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.

Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo.

UNASSIGNED: High-dose corticosteroids may be accompanied by central nervous system side-effects, including psychiatric disorders. These psychiatric disorders tend to appear relatively early in treatment. We report an unusual case of mania after long-term administration of a small dose of prednisolone.
UNASSIGNED: A patient was treated for relapsed Crohn\'s disease with a small dose of prednisolone (10 mg/day). After 6 months, she became severely manic. There was no family history of psychiatric disorders. The mania was resistant to olanzapine and sodium valproate, but improved with the reduction of the prednisolone dose. Prednisolone was tapered off while confirming with the gastroenterologist that there was no flare-up of Crohn\'s disease. She is now off prednisolone and is doing well, with no outbreaks of Crohn\'s disease or manic episodes.
UNASSIGNED: This case of severe mania after 6 months of low-dose prednisolone is unusual. Physicians should be aware that even small doses of long-term prednisolone may cause the emergence of severe mania.