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Pediatric Allergy and Immunology :... Jun 2024Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical...
BACKGROUND
Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented.
METHODS
The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control.
RESULTS
Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation.
CONCLUSION
Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.
Topics: Humans; Radiation Tolerance; Male; Female; Severe Combined Immunodeficiency; Infant; DNA-Binding Proteins; Child, Preschool; Retrospective Studies; Endonucleases; Nuclear Proteins; Child; Cohort Studies
PubMed: 38860449
DOI: 10.1111/pai.14171 -
Radiotherapy and Oncology : Journal of... Jun 2024Use of stereotactic ablative radiotherapy (SABR) for central lung tumors can result in up to a 35% incidence of late pulmonary toxicity. We evaluated an automated...
INTRODUCTION
Use of stereotactic ablative radiotherapy (SABR) for central lung tumors can result in up to a 35% incidence of late pulmonary toxicity. We evaluated an automated scoring method to quantify post-SABR bronchial changes by using artificial intelligence (AI)-based airway segmentation.
MATERIALS AND METHODS
Central lung SABR patients treated at Amsterdam UMC (AUMC, internal reference dataset) and Peter MacCallum Cancer Centre (PMCC, external validation dataset) were identified. Patients were eligible if they had pre- and post-SABR CT scans with ≤ 1 mm resolution. The first step of the automated scoring method involved AI-based airway auto-segmentation using MEDPSeg, an end-to-end deep learning-based model. The Vascular Modeling Toolkit in 3D Slicer was then used to extract a centerline curve through the auto-segmented airway lumen, and cross-sectional measurements were computed along each bronchus for all CT scans. For AUMC patients, airway stenosis/occlusion was evaluated by both visual assessment and automated scoring. Only the automated method was applied to the PMCC dataset.
RESULTS
Study patients comprised 26 from AUMC, and 33 from PMCC. Visual scoring identified stenosis/occlusion in 8 AUMC patients (31 %), most frequently in the segmental bronchi. After airway auto-segmentation, minor manual edits were needed in 9 % of patients. Segmentation for a single scan averaged 83sec (range 73-136). Automated scoring nearly doubled detected airway stenosis/occlusion (n = 15, 58 %), and allowed for earlier detection in 5/8 patients who had also visually scored changes. Estimated rates were 48 % and 66 % at 1- and 2-years, respectively, for the internal dataset. The automated detection rate was 52 % in the external dataset, with 1- and 2-year risks of 56 % and 61 %, respectively.
CONCLUSION
An AI-based automated scoring method allows for detection of more bronchial stenosis/occlusion after lung SABR, and at an earlier time-point. This tool can facilitate studies to determine early airway changes and establish more reliable airway tolerance doses.
PubMed: 38857700
DOI: 10.1016/j.radonc.2024.110376 -
PloS One 2024This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial...
This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial strains, Metabacillus halosaccharovorans (VITHBRA001) and Bacillus paralicheniformis (VITHBRA024) (D10 values 2.32 kGy and 1.42 kGy, respectively), inhabiting the top-ranking high background radiation area (HBRA) of Chavara-Neendakara placer deposit (Kerala, India). The present investigation has been carried out in the context that information on strategies of bacteria having mid-range resistance for gamma radiation is inadequate. WGS, annotation, COG and KEGG analyses and manual curation of genes helped us address the possible pathways involved in the major domains of radiation resistance, involving recombination repair, base excision repair, nucleotide excision repair and mismatch repair, and the antioxidant genes, which the candidate could activate to survive under ionizing radiation. Additionally, with the help of these data, we could compare the candidate strains with that of the extremely radiation resistant model bacterium Deinococccus radiodurans, so as to find the commonalities existing in their strategies of resistance on the one hand, and also the rationale behind the difference in D10, on the other. Genomic analysis of VITHBRA001 and VITHBRA024 has further helped us ascertain the difference in capability of radiation resistance between the two strains. Significantly, the genes such as uvsE (NER), frnE (protein protection), ppk1 and ppx (non-enzymatic metabolite production) and those for carotenoid biosynthesis, are endogenous to VITHBRA001, but absent in VITHBRA024, which could explain the former's better radiation resistance. Further, this is the first-time study performed on any bacterial population inhabiting an HBRA. This study also brings forward the two species whose radiation resistance has not been reported thus far, and add to the knowledge on radiation resistant capabilities of the phylum Firmicutes which are abundantly observed in extreme environment.
Topics: Radiation Tolerance; Genome, Bacterial; Gamma Rays; Background Radiation; Whole Genome Sequencing; India; Bacillus; DNA Repair
PubMed: 38857267
DOI: 10.1371/journal.pone.0304810 -
Journal of Immunology (Baltimore, Md. :... Jun 2024Recruitment of immune cells to the injury site plays a pivotal role in the pathology of radiation-associated diseases. In this study, we investigated the impact of the...
CCL22 Induces the Polarization of Immature Dendritic Cells into Tolerogenic Dendritic Cells in Radiation-Induced Lung Injury through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 Signaling Pathway.
Recruitment of immune cells to the injury site plays a pivotal role in the pathology of radiation-associated diseases. In this study, we investigated the impact of the chemokine CCL22 released from alveolar type II epithelial (AT2) cells after irradiation on the recruitment and functional changes of dendritic cells (DCs) in the development of radiation-induced lung injury (RILI). By examining changes in CCL22 protein levels in lung tissue of C57BL/6N mice with RILI, we discovered that ionizing radiation increased CCL22 expression in irradiated alveolar AT2 cells, as did MLE-12 cells after irradiation. A transwell migration assay revealed that CCL22 promoted the migration of CCR4-positive DCs to the injury site, which explained the migration of pulmonary CCR4-positive DCs in RILI mice in vivo. Coculture experiments demonstrated that, consistent with the response of regulatory T cells in the lung tissue of RILI mice, exogenous CCL22-induced DCs promoted regulatory T cell proliferation. Mechanistically, we demonstrated that Dectin2 and Nr4a2 are key targets in the CCL22 signaling pathway, which was confirmed in pulmonary DCs of RILI mice. As a result, CCL22 upregulated the expression of PD-L1, IL-6, and IL-10 in DCs. Consequently, we identified a mechanism in which CCL22 induced DC tolerance through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 pathway. Collectively, these findings demonstrated that ionizing radiation stimulates the expression of CCL22 in AT2 cells to recruit DCs to the injury site and further polarizes them into a tolerant subgroup of CCL22 DCs to regulate lung immunity, ultimately providing potential therapeutic targets for DC-mediated RILI.
PubMed: 38856585
DOI: 10.4049/jimmunol.2300718 -
Applied Optics Apr 2024We propose a low loss, wideband silicon transverse magnetic (TM) polarizer with high polarization extinction ratio and low reflection based on subwavelength grating. By...
We propose a low loss, wideband silicon transverse magnetic (TM) polarizer with high polarization extinction ratio and low reflection based on subwavelength grating. By arranging and optimizing a mutually perpendicular subwavelength grating with different duty cycles as the core and cladding, efficient waveguiding and radiation can be achieved for the TM and transverse electric (TE) injection, respectively. In simulation, the proposed TM polarizer has a footprint of 40µ×16.68µ, an insertion loss <0.7 , a polarization extinction ratio ≥20 , and an unwanted TE reflection <-17.4 in the wavelength range of 1230-1700 nm. Moreover, the fabrication tolerance of the proposed device is also investigated.
PubMed: 38856393
DOI: 10.1364/AO.520940 -
Applied Optics Apr 2024Orthogonal frequency division multiplexing (OFDM) utilizes numerous sub-carriers to achieve high transmission data rates. The frequency selectivity of the channel...
Orthogonal frequency division multiplexing (OFDM) utilizes numerous sub-carriers to achieve high transmission data rates. The frequency selectivity of the channel becomes a crucial factor influencing the communication performance of OFDM-based systems. In optical wireless communication (OWC) systems, the photomultiplier tube (PMT) may experience saturation when the incident optical power approaches its saturation threshold. This paper, for the first time, characterizes the saturation levels of a high-speed PMT based on the measured amplitude in the time domain and the output response of the PMT in the frequency domain. Additionally, an adaptive optical saturation compensation algorithm, leveraging an electronically controlled variable optical attenuator, is proposed to realize a reliable OWC system. Experimental results demonstrate that the proposed saturation compensation method achieves a higher tolerance to large dynamic signal and background radiation compared with that without compensation, while maintaining a satisfactory bit error rate.
PubMed: 38856372
DOI: 10.1364/AO.516465 -
Frontiers in Pharmacology 2024Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect the accumulation of radical oxygen...
INTRODUCTION
Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect the accumulation of radical oxygen species (ROS) in prostate cancer cells and . In this study, we tested its anti-cancer spectrum in multiple platforms.
METHODS
We first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity.
RESULTS
Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models.
CONCLUSION
Taken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index .
PubMed: 38855749
DOI: 10.3389/fphar.2024.1409506 -
Oral Oncology Aug 2024
Comment on "The circadian clock gene, BMAL1, promotes radiosensitization in nasopharyngeal carcinoma by inhibiting the epithelial-to-mesenchymal transition via the TGF-β1/Smads/Snail1 axis".
Topics: Humans; Nasopharyngeal Carcinoma; Epithelial-Mesenchymal Transition; Snail Family Transcription Factors; Transforming Growth Factor beta1; ARNTL Transcription Factors; Nasopharyngeal Neoplasms; Radiation Tolerance; Circadian Clocks
PubMed: 38852233
DOI: 10.1016/j.oraloncology.2024.106890 -
BMC Cancer Jun 2024This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina.
MATERIALS AND METHODS
We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion.
RESULTS
A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 Gy (95% CI: 75.3-96.6 Gy).
CONCLUSIONS
A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials.
Topics: Humans; Female; Vaginal Neoplasms; Dose-Response Relationship, Radiation; Radiotherapy Dosage; Neoplasm Recurrence, Local; Middle Aged; Treatment Outcome; Aged; Vagina
PubMed: 38851692
DOI: 10.1186/s12885-024-12486-1 -
International Journal of Radiation... Jul 2024
Topics: Humans; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Radiation Tolerance; Squamous Cell Carcinoma of Head and Neck; Tumor Hypoxia; Radiation-Sensitizing Agents; Cell Hypoxia
PubMed: 38851276
DOI: 10.1016/j.ijrobp.2024.02.055