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Cancers Apr 2024Older adults with cancer often present with distinct complexities that complicate their care, yet the language used to discuss their management at multidisciplinary...
Older adults with cancer often present with distinct complexities that complicate their care, yet the language used to discuss their management at multidisciplinary cancer conferences (MCCs) remains poorly understood. A mixed methods study was conducted at a tertiary cancer centre in Toronto, Canada, where MCCs spanning five tumour sites were attended over six months. For presentations pertaining to a patient aged 75 or older, a standardized data collection form was used to record their demographic, cancer-related, and non-cancer-related information, as well as the presenter's specialty and training level. Descriptive statistics and thematic analysis were employed to explore MCC depictions of older patients ( = 75). Frailty status was explicitly mentioned in 20.0% of presentations, but discussions more frequently referenced comorbidity burden (50.7%), age (33.3%), and projected treatment tolerance (30.7%) as surrogate measures. None of the presentations included mentions of formal geriatric assessment (GA) or validated frailty tools; instead, presenters tended to feature select GA domains and subjective descriptions of appearance ("looks to be fit") or overall health ("relatively healthy"). In general, MCCs appeared to rely on age-focused language that may perpetuate ageism. Further work is needed to investigate how frailty and geriatric considerations can be objectively incorporated into discussions in geriatric oncology.
PubMed: 38672559
DOI: 10.3390/cancers16081477 -
Life Sciences in Space Research May 2024The cortical anthraquinone yellow-orange pigment parietin is a secondary lichen substance providing UV-shielding properties that is produced by several lichen species....
The cortical anthraquinone yellow-orange pigment parietin is a secondary lichen substance providing UV-shielding properties that is produced by several lichen species. In our work, the secondary metabolite has been extracted from air-dried thalli of Xanthoria parietina. The aims of this study were to characterize parietin absorbance through UV-VIS spectrophotometry and with IR spectroscopy and to evaluate its photodegradability under UV radiation through in situ reflectance IR spectroscopy to understand to what extent the substance may have a photoprotective role. This allows us to relate parietin photo-degradability to the lichen UV tolerance in its natural terrestrial habitat and in extreme environments relevant for astrobiology such as Mars. Extracted crystals were UV irradiated for 5.59 h under N flux. After the UV irradiation, we assessed relevant degradations in the 1614, 1227, 1202, 1160 and 755 cm bands. However, in light of Xanthoria parietina survivability in extreme conditions such as space- and Mars-simulated ones, we highlight parietin UV photo-resistance and its relevance for astrobiology as photo-protective substance and possible bio-hint.
Topics: Ultraviolet Rays; Exobiology; Lichens; Emodin; Photolysis; Spectrophotometry, Infrared
PubMed: 38670647
DOI: 10.1016/j.lssr.2024.03.004 -
Journal of Applied Clinical Medical... May 2024To establish the clinical applicability of deep-learning organ-at-risk autocontouring models (DL-AC) for brain radiotherapy. The dosimetric impact of contour editing,...
PURPOSE
To establish the clinical applicability of deep-learning organ-at-risk autocontouring models (DL-AC) for brain radiotherapy. The dosimetric impact of contour editing, prior to model training, on performance was evaluated for both CT and MRI-based models. The correlation between geometric and dosimetric measures was also investigated to establish whether dosimetric assessment is required for clinical validation.
METHOD
CT and MRI-based deep learning autosegmentation models were trained using edited and unedited clinical contours. Autosegmentations were dosimetrically compared to gold standard contours for a test cohort. D1%, D5%, D50%, and maximum dose were used as clinically relevant dosimetric measures. The statistical significance of dosimetric differences between the gold standard and autocontours was established using paired Student's t-tests. Clinically significant cases were identified via dosimetric headroom to the OAR tolerance. Pearson's Correlations were used to investigate the relationship between geometric measures and absolute percentage dose changes for each autosegmentation model.
RESULTS
Except for the right orbit, when delineated using MRI models, the dosimetric statistical analysis revealed no superior model in terms of the dosimetric accuracy between the CT DL-AC models or between the MRI DL-AC for any investigated brain OARs. The number of patients where the clinical significance threshold was exceeded was higher for the optic chiasm D1% than other OARs, for all autosegmentation models. A weak correlation was consistently observed between the outcomes of dosimetric and geometric evaluations.
CONCLUSIONS
Editing contours before training the DL-AC model had no significant impact on dosimetry. The geometric test metrics were inadequate to estimate the impact of contour inaccuracies on dose. Accordingly, dosimetric analysis is needed to evaluate the clinical applicability of DL-AC models in the brain.
Topics: Humans; Deep Learning; Organs at Risk; Magnetic Resonance Imaging; Radiotherapy Dosage; Tomography, X-Ray Computed; Brain Neoplasms; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Radiometry; Image Processing, Computer-Assisted
PubMed: 38664894
DOI: 10.1002/acm2.14345 -
NPJ Microgravity Apr 2024A systematic review of literature was conducted to evaluate the effectiveness of passive countermeasures in ameliorating the cardiopulmonary and musculoskeletal effects... (Review)
Review
A systematic review of literature was conducted to evaluate the effectiveness of passive countermeasures in ameliorating the cardiopulmonary and musculoskeletal effects of gravitational unloading on humans during spaceflight. This systematic review is the third of a series being conducted by the European Space Agency to evaluate the effectiveness of countermeasures to physiologic deconditioning during spaceflight. With future long-duration space missions on the horizon, it is critical to understand the effectiveness of existing countermeasures to promote astronaut health and improve the probability of future mission success. An updated search for studies examining passive countermeasures was conducted in 2021 to supplement results from a broader search conducted in 2017 for all countermeasures. Ground-based analogue and spaceflight studies were included in the search. A total of 647 articles were screened following removal of duplicates, of which 16 were included in this review. Data extraction and analysis, quality assessment of studies, and transferability of reviewed studies to actual spaceflight based on their bed-rest protocol were conducted using dedicated tools created by the Aerospace Medicine Systematic Review Group. Of the 180 examined outcomes across the reviewed studies, only 20 were shown to have a significant positive effect in favour of the intervention group. Lower body negative pressure was seen to significantly maintain orthostatic tolerance (OT) closer to baseline as comparted to control groups. It also was seen to have mixed efficacy with regards to maintaining resting heart rate close to pre-bed rest values. Whole body vibration significantly maintained many balance-related outcome measures close to pre-bed rest values as compared to control. Skin surface cooling and centrifugation both showed efficacy in maintaining OT. Centrifugation also was seen to have mixed efficacy with regards to maintaining VO2max close to pre-bed rest values. Overall, standalone passive countermeasures showed no significant effect in maintaining 159 unique outcome measures close to their pre-bed rest values as compared to control groups. Risk of bias was rated high or unclear in all studies due to poorly detailed methodologies, poor control of confounding variables, and other sources of bias (i.e. inequitable recruitment of participants leading to a higher male:female ratios). The bed-rest transferability (BR) score varied from 2-7, with a median score of 5. Generally, most studies had good BR transferability but underreported on factors such as control of sunlight or radiation exposure, diet, level of exercise and sleep-cycles. We conclude that: (1) Lack of standardisation of outcome measurement and methodologies has led to large heterogeneity amongst studies; (2) Scarcity of literature and high risk of bias amongst existing studies limits the statistical power of results; and (3) Passive countermeasures have little or no efficacy as standalone measures against cardiopulmonary and musculoskeletal deconditioning induced by spaceflight related to physiologic deterioration due to gravity un-loading.
PubMed: 38664498
DOI: 10.1038/s41526-024-00389-1 -
The Science of the Total Environment Jun 2024Arctic fjords are considered to be one of the ecosystems changing most rapidly in response to climate change. In the Svalbard archipelago, fjords are experiencing a...
Arctic fjords are considered to be one of the ecosystems changing most rapidly in response to climate change. In the Svalbard archipelago, fjords are experiencing a shift in environmental conditions due to the Atlantification of Arctic waters and the retreat of sea-terminating glaciers. These environmental changes are predicted to facilitate expansion of large, brown macroalgae, into new ice-free regions. The potential resilience of macroalgal benthic communities in these fjord systems will depend on their response to combined pressures from freshening due to glacial melt, exposure to warmer waters, and increased turbidity from meltwater runoff which reduces light penetration. Current predictions, however, have a limited ability to elucidate the future impacts of multiple-drivers on macroalgal communities with respect to ecosystem function and biogeochemical cycling in Arctic fjords. To assess the impact of these combined future environmental changes on benthic productivity and resilience, we conducted a two-month mesocosm experiment exposing mixed kelp communities to three future conditions comprising increased temperature (+ 3.3 and + 5.3°C), seawater freshening by ∼ 3.0 and ∼ 5.0 units (i.e., salinity of 30 and 28, respectively), and decreased photosynthetically active radiation (PAR, - 25 and - 40 %). Exposure to these combined treatments resulted in non-significant differences in short-term productivity, and a tolerance of the photosynthetic capacity across the treatment conditions. We present the first robust estimates of mixed kelp community production in Kongsfjorden and place a median compensation irradiance of ∼12.5 mmol photons m h as the threshold for positive net community productivity. These results are discussed in the context of ecosystem productivity and biological tolerance of kelp communities in future Arctic fjord systems.
Topics: Climate Change; Kelp; Arctic Regions; Estuaries; Ecosystem; Svalbard; Seawater
PubMed: 38663592
DOI: 10.1016/j.scitotenv.2024.172571 -
Journal of Cancer Research and Clinical... Apr 2024Core 1β1,3-galactosyltransferase 1 (C1GALT1) exhibits elevated expression in multiple cancers. The present study aimed to elucidate the clinical significance of C1GALT1...
PURPOSE
Core 1β1,3-galactosyltransferase 1 (C1GALT1) exhibits elevated expression in multiple cancers. The present study aimed to elucidate the clinical significance of C1GALT1 aberrant expression and its impact on radiosensitivity in lung adenocarcinoma (LUAD).
METHODS
The C1GALT1 expression and its clinical relevance were investigated through public databases and LUAD tissue microarray analyses. A549 and H1299 cells with either C1GALT1 knockdown or overexpression were further assessed through colony formation, gamma-H2A histone family member X immunofluorescence, 5-ethynyl-2'-deoxyuridine incorporation, and flow cytometry assays. Bioinformatics analysis was used to explore single cell sequencing data, revealing the influence of C1GALT1 on cancer-associated cellular states. Vimentin, N-cadherin, and E-cadherin protein levels were measured through western blotting.
RESULTS
The expression of C1GALT1 was significantly higher in LUAD tissues than in adjacent non-tumor tissues both at mRNA and protein level. High expression of C1GALT1 was correlated with lymph node metastasis, advanced T stage, and poor survival, and was an independent risk factor for overall survival. Radiation notably upregulated C1GALT1 expression in A549 and H1299 cells, while radiosensitivity was increased following C1GALT1 knockdown and decreased following overexpression. Experiment results showed that overexpression of C1GALT1 conferred radioresistance, promoting DNA repair, cell proliferation, and G/M phase arrest, while inhibiting apoptosis and decreasing E-cadherin expression, alongside upregulating vimentin and N-cadherin in A549 and H1299 cells. Conversely, C1GALT1 knockdown had opposing effects.
CONCLUSION
Elevated C1GALT1 expression in LUAD is associated with an unfavorable prognosis and contributes to increased radioresistance potentially by affecting DNA repair, cell proliferation, cell cycle regulation, and epithelial-mesenchymal transition (EMT).
Topics: Humans; Adenocarcinoma of Lung; Apoptosis; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Epithelial-Mesenchymal Transition; Galactosyltransferases; Gene Expression Regulation, Neoplastic; Lung Neoplasms; Prognosis; Radiation Tolerance
PubMed: 38662050
DOI: 10.1007/s00432-024-05745-y -
Aging Apr 2024It is reported that the incidence rate and mortality of lung cancer are very high. Therefore, early diagnosis and identification of specific biomarkers are crucial for...
BACKGROUND
It is reported that the incidence rate and mortality of lung cancer are very high. Therefore, early diagnosis and identification of specific biomarkers are crucial for the clinical treatment of lung cancer. This study aims to comprehensively investigate the prognostic significance of KRT6A in human lung cancer.
METHODS
The GEO2R online tool was utilized to analyze the differential expression of mRNA between lung carcinoma tissues and radioresistant tissues in the GSE73095 and GSE197236 datasets. DAVID database was used to perform GO and KEGG enrichment analyses on target genes. The Kaplan-Meier plotter tool was used to analyze the impact of key messenger ribonucleic acid on the survival status of lung cancer. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to investigate the impact of key genes on the phenotype of lung cancer cells. After the knockout, we conducted cell migration and CCK-8 experiments to detect their effects on cell proliferation and invasion.
RESULTS
40 differentially expressed genes (DEGs) were chosen from GSE73095 and 118 DEGs were chosen from GSE197236. Kaplan-Meier map analysis showed that the overall cancer survival rate of the high-expression KRT6A group was higher than that of the low-expression group ( < 0.05). Besides, cell experiments have shown that when the KRT6A gene is downregulated, the proliferation and invasion ability of lung cancer cells is weakened.
CONCLUSIONS
Our research concluded that KRT6A may take part in the radioresistance and progression of lung cancer and can be a potential biomarker for lung cancer patients.
Topics: Humans; Lung Neoplasms; Keratin-6; Radiation Tolerance; Neoplasm Invasiveness; Signal Transduction; Gene Expression Regulation, Neoplastic; Tumor Suppressor Protein p53; Cell Movement; Cell Proliferation; Cell Line, Tumor; Prognosis; Biomarkers, Tumor; Neoplasm Metastasis
PubMed: 38656878
DOI: 10.18632/aging.205742 -
Journal of Experimental & Clinical... Apr 2024Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated...
BACKGROUND
Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear.
METHODS
RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein.
RESULTS
We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5'-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma.
CONCLUSIONS
These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma.
Topics: Humans; Nasopharyngeal Carcinoma; Rad51 Recombinase; Mice; Animals; Radiation Tolerance; Recombinational DNA Repair; RNA, Circular; Nasopharyngeal Neoplasms; Cell Line, Tumor; Female; Male; Prognosis; Mice, Nude
PubMed: 38654320
DOI: 10.1186/s13046-024-03049-0 -
Frontiers in Oncology 2024Cervical carcinoma is the most prevalent gynecology malignant tumor and ranks as the fourth most common cancer worldwide, thus posing a significant threat to the lives... (Review)
Review
Cervical carcinoma is the most prevalent gynecology malignant tumor and ranks as the fourth most common cancer worldwide, thus posing a significant threat to the lives and health of women. Advanced and early-stage cervical carcinoma patients with high-risk factors require adjuvant treatment following surgery, with radiotherapy being the primary approach. However, the tolerance of cervical cancer to radiotherapy has become a major obstacle in its treatment. Recent studies have demonstrated that radiation resistance in cervical cancer is closely associated with DNA damage repair pathways, the tumor microenvironment, tumor stem cells, hypoxia, cell cycle arrest, and epigenetic mechanisms, among other factors. The development of tumor radiation resistance involves complex interactions between multiple genes, pathways, and mechanisms, wherein each factor interacts through one or more signaling pathways. This paper provides an overview of research progress on an understanding of the mechanism underlying radiation resistance in cervical cancer.
PubMed: 38651153
DOI: 10.3389/fonc.2024.1380448 -
Cureus Mar 2024Background This study prospectively analyzed the clinical significance of tubarial glands (TGs) doses in head and neck cancer (HNC) patients. Methods Patients diagnosed...
Background This study prospectively analyzed the clinical significance of tubarial glands (TGs) doses in head and neck cancer (HNC) patients. Methods Patients diagnosed with HNC in Ankara Bilkent City Hospital, Turkey were analyzed. TGs volumes and doses were noted. The patients were evaluated in terms of acute dysphagia (AD) and radiation therapy (RT)-associated xerostomia. Results The median volume of the TGs was 3.5(2.1-5.9)cc. No increased standardized uptake values (SUV) were observed in the TGs. There was no significant relationship between TGs values and the third or sixth months of xerostomia after RT. There was a significant relationship between grade ≥2 AD and TGs-D (p0.020); TGs-V(p0.007); TGs-V(p0.009); TGs-V(p0.011); TGs-V(p0.010), TGs-V(p0.045). In terms of the risk of grade ≥2 AD, the cut-off value of the TGs-D was analyzed for 50 Gy, with 75% sensitivity and 73.3% specificity (p 0.020; AUC 0.746; 95% CI 0.561-0.929). Additionally for grade ≥2 AD, the cut-off value of the TGs-Vwas analyzed 78 with 81.3% sensitivity and 80.0% specificity (p 0.011; AUC 0.769; 95% CI 0.591-0.947). Conclusion A significant correlation was found between TGs doses and AD during RT. TGs-Vvalue showed higher significance. In future studies, the clinical significance of TGs can be studied especially on this value. The relationship between TGs doses and xerostomia should be evaluated with a larger series.
PubMed: 38646264
DOI: 10.7759/cureus.56566