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Frontiers in Oncology 2024We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two...
PURPOSE
We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two courses of intensity modulated radiotherapy (IMRT) to provide more reliable dose-volume data reference to set the temporal lobe tolerance dose for recurrent NPC patients in the future.
METHODS AND MATERIALS
Recurrent NPC patients were randomly divided into training data set and validation data set in a ratio of 2:1, All the temporal lobes (TLs) were re-contoured as R/L structures and named separately in the MIM system. The dose distribution of the initial IMRT plan was deformed into the second course planning CT via MIM software to get the deformed dose. Equivalent dose of TLs in 2Gy fractions was calculated via linear quadratic model, using an α/β=3 for temporal lobes. NTCP model that correlated the irradiated volume of the temporal lobe and? the clinical variables were evaluated in a multivariate prediction model using AUC analysis.
RESULTS
From Jan. 2010 to Dec. 2020, 78 patients were enrolled into our study. Among which 26 (33.3%) developed TLI. The most important factors affecting TLI was the sum-dose d1.5cc of TL, while the possible clinical factors did not reach statistically significant differences in multivariate analysis. According to NTCP model, the TD5 and TD50 EQD2 dose of sum-dose d1.5cc were 65.26Gy (46.72-80.69Gy) and 125.25Gy (89.51-152.18Gy), respectively. For the accumulated EQD2 dose, the area under ROC shadow was 0.8702 (0.7577-0.9828) in model validation, p<0.001.
CONCLUSION
In this study, a NTCP model of temporal lobe injury after a second course of IMRT for recurrent nasopharyngeal carcinoma was established. TD5 and TD50 doses of temporal lobe injury after re-RT were obtained according to the model, and the model was verified by validation set data.
PubMed: 38873258
DOI: 10.3389/fonc.2024.1394111 -
Environmental Monitoring and Assessment Jun 2024The Citarum watershed and the Saguling reservoir are vital natural resources in Indonesia, affecting the livelihood of West Java and the DKI Jakarta population. This...
The Citarum watershed and the Saguling reservoir are vital natural resources in Indonesia, affecting the livelihood of West Java and the DKI Jakarta population. This study aimed to assess the soil erosion in the Upper Citarum watershed and identify its source. The study used the fallout radionuclide technique, geochemical tracers, and an unmixing model to measure soil erosion and the contribution of suspended sediment sources due to erosion. Soil bulk transects and surface soil were sampled using a coring tool on the Ciwidey and Cisangkuy sub-watersheds. Riverbank and suspended sediment samples were collected from tributaries and rivers. With Cs, 40% of the samples had values below the minimum detectable activity, and vice versa for Pb, all samples are detectable. For mitigation, bare land needs to be recovered due to its erosion (25.6 t ha year) exceeding the tolerance erosion value (17 t ha year). Statistically, Mg and Na were the most appropriate composite tracers for suspended sediment contribution. The unmixing model predicted the sediment contributors from bare land (58%), the riverbank (32.7%), and plantation land (9.3%). Proper land conservation could reduce sediment supply by almost 14.7% and extend the reservoir's life. This is the first study to report the feasibility of the unmixing model in Indonesia.
Topics: Indonesia; Environmental Monitoring; Rivers; Soil Erosion; Geologic Sediments; Soil; Cesium Radioisotopes; Conservation of Natural Resources
PubMed: 38871834
DOI: 10.1007/s10661-024-12750-8 -
International Journal of Radiation... 2024Bertoni is a perennial herb, widely used as a natural sweetener around the globe. The key compounds responsible for its sweetness includes stevioside and...
PURPOSE
Bertoni is a perennial herb, widely used as a natural sweetener around the globe. The key compounds responsible for its sweetness includes stevioside and rebaudioside-A. In order to improve these steviol glycosides, the present study was initiated to study the effect of induced mutagenesis on growth parameters, steviol glycosides and nuclear DNA content in Bertoni using ten doses of gamma-rays (5-100 kR).
MATERIALS AND METHODS
Healthy seeds of '' variety of Bertoni developed and maintained at stevia breeding farm, Agrotechnology division, CSIR-Institute of Himalayan Bioresource Technology, Palampur (HP), India were irradiated with ten doses of gamma rays (600 seeds each/dose) ranging from 5 kR to 100 kR (i.e., 5, 10, 15, 20, 30, 40, 50, 60, 80 and 100 kR) using Co gamma irradiation chamber at CCS Haryana Agricultural University, Hisar, (Haryana), India.
RESULTS
Significant variations were recorded for all the seedling traits studied while major impact was noticed on the seedling after reaching the cotyledonary stage and doses above 40 kR showed absolute mortality of the seedlings. Based on probit analysis, the optimum LD dose lies in the range of 20-23 kR. Glycosidic profiling of 296 mutants using high-performance liquid chromatography showed decreased total steviol glycoside content with increased radiation dose. Doses 5 kR and 10 kR, were found to be effective in increasing the overall glycosidic content. A total of 72 promising mutants were also screened for increased rebaudioside-A stevioside ratio. Comparison of nuclear DNA content using flow cytometry revealed a similar decrease in the total nuclear DNA content with increase in dosage of gamma rays. The average genome size at 5, 10, 15, 20 and 30 kR treatments were 2.72, 2.69, 2.68, 2.70 and 2.66 pg as compared to 2.72 pg in control.
CONCLUSIONS
Mild dose of gamma rays (5 and 10 kR) in stevia were found to be effective in improving the mean steviol glycoside content and may be used in future stevia mutation programmes.
Topics: Stevia; Diterpenes, Kaurane; Gamma Rays; Radiation Tolerance; Glucosides; Dose-Response Relationship, Radiation
PubMed: 38870412
DOI: 10.1080/09553002.2024.2362647 -
Nano Letters Jun 2024Radiation-tolerance and repairable flexible transistors and integrated circuits (ICs) with low power consumption have become hot topics due to their wide applications in...
Radiation-tolerance and repairable flexible transistors and integrated circuits (ICs) with low power consumption have become hot topics due to their wide applications in outer space, nuclear power plants, and X-ray imaging. Here, we designed and developed novel flexible semiconducting single-walled carbon nanotube (sc-SWCNT) thin-film transistors (TFTs) and ICs. Sc-SWCNT solid-electrolyte-gate dielectric (SEGD) TFTs showcase symmetric ambipolar characteristics with flat-band voltages (V) of ∼0 V, high I/I ratios (>10), and the recorded irradiation resistance (up to 22 Mrad). Moreover, flexible sc-SWCNT ICs, including CMOS-like inverters and NAND and NOR logic gates, have excellent operating characteristics with low power consumption (≤8.4 pW) and excellent irradiation resistance. Significantly, sc-SWCNT SEGD TFTs and ICs after radiation with a total irradiation dose (TID) ≥ 11 Mrad can be repaired after thermal heating at 100 °C. These outstanding characteristics are attributed to the designed device structures and key core materials including SEGD and sc-SWCNT.
PubMed: 38869197
DOI: 10.1021/acs.nanolett.4c01691 -
Strahlentherapie Und Onkologie : Organ... Jun 2024Pulmonary artery intimal sarcoma (PAIS) is a rare and aggressive malignancy originating from the intimal layer of the pulmonary artery with poor prognosis due to its...
Pulmonary artery intimal sarcoma (PAIS) is a rare and aggressive malignancy originating from the intimal layer of the pulmonary artery with poor prognosis due to its aggressive nature. The management of PAIS poses both diagnostic and therapeutic challenges. It presents with nonspecific symptoms and is often misdiagnosed as pulmonary embolism. While surgical resection is the primary treatment modality, the role of adjuvant chemotherapy and radiotherapy remains uncertain. However, given the high recurrence rate, adjuvant chemotherapy and/or radiotherapy have been utilized in a limited number of case reports. We present the case of a 46-year-old woman who was diagnosed with PAIS and underwent surgical resection followed by adjuvant chemotherapy (ChT) and radiotherapy (RT), demonstrating good tolerance to this multimodal treatment approach.
PubMed: 38866999
DOI: 10.1007/s00066-024-02250-6 -
Nature Communications Jun 2024Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT...
Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT (Cas12a-based One-for-all High-speed Isothermal Test), a one-pot CRISPR-based assay for indel detection. Leveraging an engineered AsCas12a protein variant with high mismatch tolerance and broad PAM scope, CoHIT can use a single crRNA to detect multiple NPM1 gene c.863_864 4-bp insertions in acute myeloid leukemia (AML). After optimizing multiple parameters, CoHIT achieves a detection limit of 0.01% and rapid results within 30 minutes, without wild-type cross-reactivity. It successfully identifies NPM1 mutations in 30 out of 108 AML patients and demonstrates potential in monitoring minimal residual disease (MRD) through continuous sample analysis from three patients. The CoHIT method is also competent for detecting indels of KIT, BRAF, and EGFR genes. Integration with lateral flow test strips and microfluidic chips highlights CoHIT's adaptability and multiplexing capability, promising significant advancements in clinical cancer diagnostics.
Topics: Humans; Leukemia, Myeloid, Acute; INDEL Mutation; CRISPR-Cas Systems; Nucleophosmin; Neoplasm, Residual; Nuclear Proteins; Proto-Oncogene Proteins B-raf; Genetic Testing; ErbB Receptors; Bacterial Proteins; Endodeoxyribonucleases; CRISPR-Associated Proteins
PubMed: 38866774
DOI: 10.1038/s41467-024-49414-7 -
Advances in Immunology 2024The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from... (Review)
Review
The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from food antigen, gut microbiome, metabolic waste products, and dead cell debris. Within the intestine, most T cells are found in three primary compartments: the organized gut-associated lymphoid tissue, the lamina propria, and the epithelium. The well-orchestrated epithelial-immune-microbial interaction is critically important for the precise immune response. The main role of intestinal mesenchymal stromal cells is to support a structural framework within the gut wall. However, recent evidence from stromal cell studies indicates that they also possess significant immunomodulatory functions, such as maintaining intestinal tolerance via the expression of PDL1/2 and MHC-II molecules, and promoting the development of CD103 dendritic cells, and IgA plasma cells, thereby enhancing intestinal homeostasis. In this review, we will summarize the current understanding of CD8 T cells and stromal cells alongside the intestinal tract and discuss the reciprocal interactions between T subsets and mesenchymal stromal cell populations. We will focus on how the tissue residency, migration, and function of CD8 T cells could be potentially regulated by mesenchymal stromal cell populations and explore the molecular mediators, such as TGF-β, IL-33, and MHC-II molecules that might influence these processes. Finally, we discuss the potential pathophysiological impact of such interaction in intestine hemostasis as well as diseases of inflammation, infection, and malignancies.
Topics: Humans; Mesenchymal Stem Cells; Animals; CD8-Positive T-Lymphocytes; Homeostasis; Intestinal Mucosa; Cell Communication; Intestines
PubMed: 38866438
DOI: 10.1016/bs.ai.2024.02.001 -
Applied and Environmental Microbiology Jun 2024The extremophile maintains a highly organized and condensed nucleoid as its default state, possibly contributing to its high tolerance to ionizing radiation (IR)....
The extremophile maintains a highly organized and condensed nucleoid as its default state, possibly contributing to its high tolerance to ionizing radiation (IR). Previous studies of the nucleoid were limited by reliance on manual image annotation and qualitative metrics. Here, we introduce a high-throughput approach to quantify the geometric properties of cells and nucleoids using confocal microscopy, digital reconstructions of cells, and computational modeling. We utilize this novel approach to investigate the dynamic process of nucleoid condensation in response to IR stress. Our quantitative analysis reveals that at the population level, exposure to IR induced nucleoid compaction and decreased the size of cells. Morphological analysis and clustering identified six distinct sub-populations across all tested experimental conditions. Results indicate that exposure to IR induced fractional redistributions of cells across sub-populations to exhibit morphologies associated with greater nucleoid condensation and decreased the abundance of sub-populations associated with cell division. Nucleoid-associated proteins (NAPs) may link nucleoid compaction and stress tolerance, but their roles in regulating compaction in are unknown. Imaging of genomic mutants of known and suspected NAPs that contribute to nucleoid condensation found that deletion of nucleic acid-binding proteins, not previously described as NAPs, can remodel the nucleoid by driving condensation or decondensation in the absence of stress and that IR increased the abundance of these morphological states. Thus, our integrated analysis introduces a new methodology for studying environmental influences on bacterial nucleoids and provides an opportunity to further investigate potential regulators of nucleoid condensation.IMPORTANCE, an extremophile known for its stress tolerance, constitutively maintains a highly condensed nucleoid. Qualitative studies have described nucleoid behavior under a variety of conditions. However, a lack of quantitative data regarding nucleoid organization and dynamics has limited our understanding of the regulatory mechanisms controlling nucleoid organization in . Here, we introduce a quantitative approach that enables high-throughput quantitative measurements of subcellular spatial characteristics in bacterial cells. Applying this to wild-type or single-protein-deficient populations of subjected to ionizing radiation, we identified significant stress-responsive changes in cell shape, nucleoid organization, and morphology. These findings highlight this methodology's adaptability and capacity for quantitatively analyzing the cellular response to stressors for screening cellular proteins involved in bacterial nucleoid organization.
PubMed: 38864629
DOI: 10.1128/aem.00108-24 -
Pest Management Science Jun 2024The diamondback moth (DBM) (Plutella xylostella) causes large losses to global crop production. Conventional insecticides are losing effectiveness due to resistance....
Phenotypic and genotypic characterization of fifty strains of Beauveria spp. (Ascomycota, Cordycipitaceae) fungal entomopathogens from diverse geographic origins against the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).
BACKGROUND
The diamondback moth (DBM) (Plutella xylostella) causes large losses to global crop production. Conventional insecticides are losing effectiveness due to resistance. Consequently, there is a growing interest in sustainable control methods like entomopathogenic fungi (EPF) in Integrated Pest Management. However, the field efficacy of fungi varies due to environmental influences. In this study, a group of 50 Beauveria strains sourced from different locations were characterized by genotype and phenotype with respect to their conidial production, temperature and UV-B radiation tolerance, and virulence against DBM.
RESULTS
Phylogenetic analysis revealed two distinct species: Beauveria bassiana (84%) and B. pseudobassiana (16%). Most strains showed optimal growth between 25 °C and 28 °C, with germination severely affected at 10 °C and 33 °C. Notably, 44% displayed high resistance to UV-B radiation (5.94 kJ m), with germination rates between 60.9% and 88.1%. Geographical origin showed no correlation with temperature or UV radiation tolerance. In virulence experiments, 52% of strains caused mortality rates exceeding 80% in DBM second instars at 7 days after exposure to a 4 mL conidial suspension (10 conidia/mL).
CONCLUSION
Survival under environmental conditions is crucial for EPF-based commercial products against DBM. Results suggest strain tolerance to environmental stressors is more tied to specific micro-climatic factors than geographical origin. Each strain exhibited unique characteristics; for example, the most virulent strain (#29) was highly UV-sensitive. Therefore, characterizing diverse strains provides essential genotypic and phenotypic insights, which are fundamental for understanding their role as biocontrol agents while facilitating efficient biopesticide product development and uptake. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
PubMed: 38864555
DOI: 10.1002/ps.8230 -
Journal of Experimental & Clinical... Jun 2024Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and...
BACKGROUND
Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment.
METHODS
Gene expression analysis was performed to look at genes upregulated in TNBC patient samples compared to other subtypes. Cell proliferation and clonogenic survivals assays determined the IC of BUB1 inhibitor (BAY1816032) and radiation enhancement ratio (rER) with pharmacologic and genomic BUB1 inhibition. Mammary fat pad xenografts experiments were performed in CB17/SCID. The mechanism through which BUB1 inhibitor sensitizes TNBC cells to radiotherapy was delineated by γ-H2AX foci assays, BLRR, Immunoblotting, qPCR, CHX chase, and cell fractionation assays.
RESULTS
BUB1 is overexpressed in BC and its expression is considerably elevated in TNBC with poor survival outcomes. Pharmacological or genomic ablation of BUB1 sensitized multiple TNBC cell lines to cell killing by radiation, although breast epithelial cells showed no radiosensitization with BUB1 inhibition. Kinase function of BUB1 is mainly accountable for this radiosensitization phenotype. BUB1 ablation also led to radiosensitization in TNBC tumor xenografts with significantly increased tumor growth delay and overall survival. Mechanistically, BUB1 ablation inhibited the repair of radiation-induced DNA double strand breaks (DSBs). BUB1 ablation stabilized phospho-DNAPKcs (S2056) following RT such that half-lives could not be estimated. In contrast, RT alone caused BUB1 stabilization, but pre-treatment with BUB1 inhibitor prevented stabilization (t, ~8 h). Nuclear and chromatin-enriched fractionations illustrated an increase in recruitment of phospho- and total-DNAPK, and KAP1 to chromatin indicating that BUB1 is indispensable in the activation and recruitment of non-homologous end joining (NHEJ) proteins to DSBs. Additionally, BUB1 staining of TNBC tissue microarrays demonstrated significant correlation of BUB1 protein expression with tumor grade.
CONCLUSIONS
BUB1 ablation sensitizes TNBC cell lines and xenografts to RT and BUB1 mediated radiosensitization may occur through NHEJ. Together, these results highlight BUB1 as a novel molecular target for radiosensitization in women with TNBC.
Topics: Humans; Triple Negative Breast Neoplasms; Animals; Female; Mice; Radiation Tolerance; Cell Line, Tumor; DNA End-Joining Repair; Protein Serine-Threonine Kinases; Xenograft Model Antitumor Assays; Cell Proliferation; Gene Expression Regulation, Neoplastic; Mice, SCID
PubMed: 38863037
DOI: 10.1186/s13046-024-03086-9