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1.
Bioact Mater ; 43: 240-254, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39386223

ABSTRACT

Ferroptosis plays a crucial role in the progression of diabetic wounds, suggesting potential therapeutic strategies to target ferroptosis. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli. Cinnamaldehyde (CA) is a specific TRPA1 agonist. In in vitro experiments, we observed that high glucose (HG) treatment induced endothelial cell ferroptosis, impairing cell function. CA successfully inhibited endothelial cell ferroptosis, improving migration, proliferation, and tube formation. Further mechanistic studies showed that CA-activated TRPA1-induced Ca2+ influx promoted the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-E 2-related factor 2 (Nrf2) translocation, which contributed to the elevation of glutathione peroxidase 4 (GPX4), leading to the inhibition of endothelial cell ferroptosis. In addition, CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel (CA@HA-Gel), allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner. The results showed that CA@HA-Gel inhibited wound endothelial cell ferroptosis and significantly promoted diabetic wound healing. In summary, the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.

2.
BMC Neurol ; 24(1): 375, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39375614

ABSTRACT

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited vascular disorder that can involve multiple organs, thus can be associated with so many clinical departments that proper screening and diagnosis of HHT are needed for providing better management of both patients and their family members. CASE PRESENTATION: We present a 58-year-old female patient with recurrent paradoxical brain embolism due to HHT. She received aspirin therapy and underwent pulmonary arteriovenous malformation embolization, recovering well and discharged 3 days postoperatively. Though ischemic stroke caused by HHT-induced vascular disorders has been reported, our patient presented with both recurrent paradoxical brain embolisms and radiologic findings of bilateral globus pallidus manganese deposition at the same time, a combination rarely reported. We also review the literature on the clinical features and management of HHT for prompt diagnosis of this genetic disease behind paradoxical embolism. CONCLUSIONS: When patients with ischemic stroke, especially recurrent ischemic stroke, have combined arteriovenous malformations (AVMs) in single or multiple organs, or clues for AVMs like manganese deposition in globus pallidus, genetic diseases such as HHT may be the reason for ischemic stroke and shouldn't be missed in the evaluation of embolic sources.


Subject(s)
Ischemic Stroke , Manganese , Telangiectasia, Hereditary Hemorrhagic , Humans , Female , Telangiectasia, Hereditary Hemorrhagic/complications , Middle Aged , Ischemic Stroke/complications , Ischemic Stroke/diagnostic imaging , Basal Ganglia/diagnostic imaging , Basal Ganglia/pathology , Recurrence , Embolism, Paradoxical/complications , Embolism, Paradoxical/diagnostic imaging
3.
BMC Infect Dis ; 24(1): 915, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232642

ABSTRACT

BACKGROUND: This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker. METHODS: Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon ß (IFN-ß) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package. RESULTS: The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P < 0.05), in patients with active lesions than in patients with stable lesions. The serum concentration of IFN-ß was significantly higher in patients with active lesions (P = 0.028). Compared with healthy individuals, the expression level of the cGAS-STING pathway was elevated in PBMCs of TB patients (P < 0.05), and the difference in the expression level of IFN-ß was not statistically significant (P > 0.05), and the serum IFN-ß concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-ß in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively. CONCLUSIONS: The expression level of TBK1 and IRF3 in PBMCs, and IFN-ß in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-ß in serum has higher sensitivity when used to differentiate between patients with active and stable lesions.


Subject(s)
Interferon Regulatory Factor-3 , Leukocytes, Mononuclear , Membrane Proteins , Nucleotidyltransferases , Tuberculosis, Spinal , Humans , Leukocytes, Mononuclear/metabolism , Male , Female , Adult , Membrane Proteins/blood , Membrane Proteins/genetics , Middle Aged , Nucleotidyltransferases/genetics , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon Regulatory Factor-3/blood , Tuberculosis, Spinal/blood , Tuberculosis, Spinal/genetics , Interferon-beta/blood , Signal Transduction , Protein Serine-Threonine Kinases/genetics , Biomarkers/blood , Prospective Studies , Young Adult , Aged
4.
BMC Health Serv Res ; 24(1): 1121, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39334368

ABSTRACT

BACKGROUND: Central venous catheters (CVC) are used for dialysis in end-stage renal disease patients, presenting a significant risk for Catheter-Related Bloodstream Infections (CRBSI). While Lean Six Sigma has been effective in reducing CRBSI, its efficacy outside intensive care units (ICU) remains less explored. This study aims to evaluate the effectiveness of Lean Six Sigma in mitigating CRBSI risks among non-ICU hemodialysis patients. METHODS: The study was conducted in a nephrology department, focusing on patients undergoing hemodialysis with temporary CVC from February to December 2021. The Lean Six Sigma method, using Define-Measure-Analyze-Improve-Control (DMAIC) methodology, was implemented in 2022 to reduce CRBSI incidence. The 2021 CRBSI rate served as the benchmark, with a goal to reduce it by the end of 2022. Value-stream mapping, Fishbone Diagrams, and Root Cause Analysis identified potential CRBSI causes. After implementing targeted improvements, CRBSI rates before and after the intervention were compared. RESULTS: The Lean Six Sigma method significantly decreased CRBSI incidence from 12.79 to 2.32 per 1,000 catheter-days following the implementation of targeted interventions ([Formula: see text]=4.60, P = 0.05). This improvement was observed comparing February-December 2021 with January-December 2022. CONCLUSION: The findings demonstrate the effectiveness of the Lean Six Sigma method in non-ICU settings, suggesting broader applicability in hemodialysis patient care.


Subject(s)
Catheter-Related Infections , Quality Improvement , Renal Dialysis , Total Quality Management , Humans , Catheter-Related Infections/prevention & control , Catheter-Related Infections/epidemiology , Kidney Failure, Chronic/therapy , Male , Central Venous Catheters/adverse effects , Incidence , Female , Catheterization, Central Venous/adverse effects , Middle Aged
5.
6.
Mikrochim Acta ; 191(10): 626, 2024 09 26.
Article in English | MEDLINE | ID: mdl-39325066

ABSTRACT

With the advancement of nanotechnology, various types of nanomaterials have been integrated into electrochemical immunoelectrodes to enhance their performance. Among these, MXene stands out as a promising candidate due to its high electron transfer capacity and abundant surface chemical groups. However, the improvement in electrode performance is often hindered by the self-restacking and agglomeration of MXene. To address this issue, multi-walled carbon nanotubes (MWCNTs) were selected to form composites with MXene. Subsequently, a label-free immunosensor, BSA/Ab/AuNPs/MXene-MWCNTs-Nafion/ITO, was fabricated for specific detection of carcinoembryonic antigen (CEA), a widely used tumor marker. The results demonstrated that the incorporation of MWCNTs can effectively prevent the self-stacking of MXene. Moreover, the composites enhanced the loading of gold nanoparticles (AuNPs) to connect the antibodies, thereby improving electronic transmission signals and sensitivity. The sensor exhibited excellent analytical performance towards CEA with a wide linear range (0.050 to 200 ng mL-1) and a low limit of detection of 0.015 ng mL-1 (S/N = 3). The possibility of it being applied in clinical trials was verified by using ELISA and differential pulse voltammetry (DPV) assays to detect CEA in serum samples. The recoveries ranged from 95.34 to 102.09% with relative standard deviations (RSDs) below 5.00%. Furthermore, the sensor displayed satisfactory selectivity, repeatability, and stability. We hope the findings highlight promising prospects for advanced immunosensor development and alternative strategies in cancer diagnosis.


Subject(s)
Biosensing Techniques , Carcinoembryonic Antigen , Electrochemical Techniques , Gold , Limit of Detection , Metal Nanoparticles , Nanotubes, Carbon , Carcinoembryonic Antigen/blood , Carcinoembryonic Antigen/immunology , Nanotubes, Carbon/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Electrochemical Techniques/methods , Humans , Biosensing Techniques/methods , Immunoassay/methods , Antibodies, Immobilized/immunology
7.
Digit Health ; 10: 20552076241277027, 2024.
Article in English | MEDLINE | ID: mdl-39193314

ABSTRACT

Objective: Explainable machine learning (XAI) was introduced in this study to improve the interpretability, explainability and transparency of the modelling results. The survex package in R was used to interpret and compare two survival models - the Cox proportional hazards regression (coxph) model and the random survival forest (rfsrc) model - and to estimate overall survival (OS) and its determinants in heart failure (HF) patients using these models. Methods: We selected 1159 HF patients hospitalised at the First Affiliated Hospital of Kunming Medical University. First, the performance of the two models was investigated using the C-index, the integrated C/D AUC, and the integrated Brier score. Second, a global explanation of the whole cohort was carried out using the time-dependent variable importance and the partial dependence survival profile. Finally, the SurvSHAP(t) and SurvLIME plots and the ceteris paribus survival profile were used to obtain a local explanation for each patient. Results: By comparing the C-index, the C/D AUC, and the Brier score, this study showed that the model performance of rfsrc was better than coxph. The global explanation of the whole cohort suggests that the C-reactive protein, lg BNP (brain natriuretic peptide), estimated glomerular filtration rate, albumin, age and blood chloride were significant unfavourable predictors of OS in HF patients in both the cxoph and the rfsrc models. By including individual patients in the model, we can provide a local explanation for each patient, which guides the clinician in individualising the patient's treatment. Conclusion: By comparison, we conclude that the model performance of rfsrc is better than that of coxph. These two predictive models, which address not only the whole population but also selected patients, can help clinicians personalise the treatment of each HF patient according to his or her specific situation.

8.
Bioelectrochemistry ; 160: 108787, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39098083

ABSTRACT

A sandwich-type electrochemical immunosensor was proposed for the ultra-sensitive detection of CD44, a potential biomarker for breast cancer. In this design, a customized template-based ionic liquid (1-butyl-2,3-dimethylimidazolium tetrafluoroborate) carbon paste electrode (CILE) served as the sensing platform, and thionine/Au nanoparticles/covalent-organic frameworks (THI/Au/COF) were used as the signal label. Moreover, an enzyme-free signal amplification strategy was introduced by involving H2O2 and phosphotungstate (PW12) with peroxidase-like activity. Under optimized conditions, the linear range is as wide as six orders of magnitude, and the detection limit is as low as 0.71 pg mL-1 (estimated based on S/N = 3). Average recoveries range from 98.16 %-100.1 %, with a relative standard deviation (RSD) of 1.42-8.27 % in mouse serum, and from 98.44 %-99.06 %, with an RSD of 1.14-4.84 % (n = 3) in artificial saliva. Furthermore, the immunosensor exhibits excellent specificity toward CD44, good stability, and low cost, indicating great potential for application in clinical trials.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Hyaluronan Receptors , Limit of Detection , Electrochemical Techniques/methods , Biosensing Techniques/methods , Humans , Immunoassay/methods , Animals , Phosphotungstic Acid/chemistry , Mice , Catalysis , Gold/chemistry , Metal Nanoparticles/chemistry , Ionic Liquids/chemistry , Electrodes , Hydrogen Peroxide/chemistry , Metal-Organic Frameworks/chemistry
9.
J Radiosurg SBRT ; 9(2): 145-156, 2024.
Article in English | MEDLINE | ID: mdl-39087064

ABSTRACT

Purpose: To compare plan quality among photon volumetric arc therapy (VMAT), Gamma Knife, and three different proton beam modalities. Methods: Fifty-five brain lesions from 20 patients were planned with three different proton spot size ranges of cyclotron-generated proton beams, CPBs (spot size σ: 2.7-7.0 mm), linear accelerator proton beams, LPBs (σ: 2.9-5.5 mm), and linear accelerator proton minibeams, LPMBs (σ: 0.9-3.9 mm), with and without apertures and compared against photon VMAT and Gamma Knife plans. Dose coverage to each lesion for each proton and photon plan was set to 99% of the GTV receiving the prescription (Rx) dose. All proton plans used ±2 mm setup uncertainty and ±2% range uncertainty in robust evaluation to achieve V100%Rx > 95% of the GTV. Apertures were applied to proton beams irradiating tumors <1 cm3 volume and located <2.5 cm depth. Conformity index (CI), gradient index (GI), V12 Gy, V4.5 Gy, and mean brain dose were compared across all plan types. The Wilcoxon signed rank test was utilized to determine statistical significance of dosimetric results compared between photon and proton plans. Results: When compared to CPB generated plans, average CI and GI were significantly better for the LPB and LPMB plans. Aperture-based IMPT plans showed improvement from Gamma Knife for all dosimetric metrics. Aperture-based IMPT plans also showed improvement in all dosimetric metrics for shallow tumors (d < 2.5 cm) when compared with non-aperture-based plans. Conclusion: The LPB and LPMB stand as excellent alternatives to CPB or photon therapy and significantly increase the preservation of normal tissue.

10.
Chem Sci ; 15(26): 10002-10009, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38966370

ABSTRACT

Bench-stable 3,3-difluoroallyl sulfonium salts (DFASs), featuring tunable activity and their editable C-ß and gem-difluoroallyl group, proved to be versatile fluoroalkylating reagents for site-selective S-gem-difluoroallylation of cysteine residues in unprotected peptides. The reaction proceeds with high efficiency under mild conditions (ambient temperature and aqueous and weak basic conditions). Various protected/unprotected peptides, especially bioactive peptides, are site-selectively S-gem-difluoroallylated. The newly added gem-difluoroallyl group and other functional groups derived from C-ß of DFASs are poised for ligation with bio-functional groups through click and radical chemistry. This stepwise "doubly orthogonal" modification of peptides enables the construction of bioconjugates with enhanced complexity and functionality. This proof of principle is successfully applied to construct a peptide-saccharide-biotin chimeric bioconjugate, indicating its great potential application in medicinal chemistry and chemical biology.

11.
Pharmacol Res ; 207: 107313, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39025169

ABSTRACT

Acute ischemic stroke (AIS) is the most prevalent type of stroke, and due to its high incidence, disability rate, and mortality rate, it imposes a significant burden on the health care system. Amino acids constitute one of the most crucial metabolic products within the human body, and alterations in their metabolic pathways have been identified in the microenvironment of AIS, thereby influencing the pathogenesis, severity, and prognosis of AIS. The amino acid metabolism characteristics in AIS are complex. On one hand, the dynamic progression of AIS continuously reshapes the amino acid metabolism pattern. Conversely, changes in the amino acid metabolism pattern also exert a double-edged effect on AIS. This interaction is bidirectional, dynamic, heterogeneous, and dose-specific. Therefore, the distinctive metabolic reprogramming features surrounding amino acids during the AIS process are systematically summarized in this paper, aiming to provide potential investigative strategies for the early diagnosis, treatment approaches, and prognostic enhancement of AIS.


Subject(s)
Amino Acids , Ischemic Stroke , Humans , Amino Acids/metabolism , Ischemic Stroke/metabolism , Animals
12.
Nature ; 631(8020): 319-327, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38898275

ABSTRACT

Naturally occurring (native) sugars and carbohydrates contain numerous hydroxyl groups of similar reactivity1,2. Chemists, therefore, rely typically on laborious, multi-step protecting-group strategies3 to convert these renewable feedstocks into reagents (glycosyl donors) to make glycans. The direct transformation of native sugars to complex saccharides remains a notable challenge. Here we describe a photoinduced approach to achieve site- and stereoselective chemical glycosylation from widely available native sugar building blocks, which through homolytic (one-electron) chemistry bypasses unnecessary hydroxyl group masking and manipulation. This process is reminiscent of nature in its regiocontrolled generation of a transient glycosyl donor, followed by radical-based cross-coupling with electrophiles on activation with light. Through selective anomeric functionalization of mono- and oligosaccharides, this protecting-group-free 'cap and glycosylate' approach offers straightforward access to a wide array of metabolically robust glycosyl compounds. Owing to its biocompatibility, the method was extended to the direct post-translational glycosylation of proteins.


Subject(s)
Chemistry Techniques, Synthetic , Oligosaccharides , Sugars , Free Radicals/chemistry , Free Radicals/metabolism , Glycosylation/radiation effects , Indicators and Reagents/chemistry , Light , Oligosaccharides/chemical synthesis , Oligosaccharides/chemistry , Oligosaccharides/metabolism , Oligosaccharides/radiation effects , Stereoisomerism , Sugars/chemical synthesis , Sugars/chemistry , Sugars/metabolism , Sugars/radiation effects
13.
Cancers (Basel) ; 16(11)2024 May 25.
Article in English | MEDLINE | ID: mdl-38893130

ABSTRACT

The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was conducted on 203 glioblastoma (GBM) patients enrolled in NRG-BN001 and 70 nasopharyngeal carcinoma (NPC) patients enrolled in NRG-HN001. For each trial, fifty high-quality photon plans were utilized to build a KBP photon model. A KBP proton model was generated using intensity-modulated proton therapy (IMPT) plans generated on 50 patients originally treated with photon RT. These models were then applied to generate KBP plans for the remaining patients, which were compared against the submitted plans for quality evaluation, including in terms of protocol compliance, target coverage, and organ-at-risk (OAR) doses. RT plans generated by the KBP models were demonstrated to have superior quality compared to the submitted plans. KBP IMPT plans can decrease the variation of proton plan quality and could possibly be used as a tool for developing improved plans in the future. Additionally, the KBP tool proved to be an effective instrument for RT plan QA in multi-center clinical trials.

15.
Front Public Health ; 12: 1391036, 2024.
Article in English | MEDLINE | ID: mdl-38912267

ABSTRACT

Introduction: The outbreak of the Coronavirus Disease 2019 pandemic has presented significant difficulties for healthcare workers worldwide, resulting in a higher tendency to quit their jobs. This study aims to investigate the correlation between organizational support, work-family-self balance, job satisfaction, and turnover intention of healthcare professionals in China's public hospitals. Methods: A cross-sectional survey was conducted on 5,434 health workers recruited from 15 public hospitals in Foshan municipality in China's Guangdong province. The survey was measured by organizational support, work-family-self balance, job satisfaction, and turnover intention using a five-point Likert scale. The association between organizational support, work-family-self balance, job satisfaction, and turnover intention was investigated using Pearson correlation analysis and mediation analysis through the PROCESS macro (Model 6). Results: Organizational support indirectly affected turnover intention through three pathways: the mediating role of work-family-self balance, job satisfaction, and the chain mediating role of both work-family-self balance and job satisfaction. Conclusion: Health administrators and relevant government sectors should provide sufficient organizational support, enhance work-family-self balance and job satisfaction among healthcare workers, and consequently reduce their turnover intentions.


Subject(s)
COVID-19 , Health Personnel , Intention , Job Satisfaction , Personnel Turnover , Humans , Personnel Turnover/statistics & numerical data , China , Cross-Sectional Studies , Male , Female , Adult , Health Personnel/psychology , Health Personnel/statistics & numerical data , Surveys and Questionnaires , Middle Aged , Hospitals, Public/statistics & numerical data , Organizational Culture
16.
Med Phys ; 51(6): 3985-3994, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38683935

ABSTRACT

BACKGROUND: Pencil beam scanning (PBS) proton therapy for moving targets is known to be impacted by interplay effects between the scanning beam and organ motion. While respiratory motion in the thoracic region is the major cause for organ motion, interplay effects depend on the delivery characteristics of proton accelerators. PURPOSE: To evaluate the impact of different types of PBS proton accelerators and spot sizes on interplay effects, mitigations, and plan quality for Stereotactic Body Radiation Therapy (SBRT) treatment of non-small cell lung cancer (NSCLC). METHODS: Twenty NSCLC patients treated with photon SBRT were selected to represent varying tumor volumes and respiratory motion amplitudes (median: 0.6 cm with abdominal compression) for this retrospective study. For each patient, plans were created using: (1) cyclotron-generated proton beams (CPB) with spot sizes of σ = 2.7-7.0 mm; (2) linear accelerator proton beams (LPB) (σ = 2.9-5.5 mm); and (3) linear accelerator proton minibeams (LPMB) (σ = 0.9-3.9 mm). The energy switching time is one second for CPB, and 0.005 s for LPMB and LPB. Plans were robustly optimized on the gross tumor volume (GTV) using each individual phase of four-dimensional computed tomography (4DCT) scans. Initially, single-field optimization (SFO) plans were evaluated; if the plan quality did not meet the dosimetric requirement, multi-field optimization (MFO) was used. MFO plans were created for all patients for comparisons. For each patient, all plans were normalized to have the same dose received by 99% of the GTV. Interplay effects were evaluated by computing the dose on 10 breathing phases, based on the spot distribution. Volumetric repainting (VR) was performed 2-6 times for each plan. We compared volume receiving 100% of the prescribed dose (V100%RX) of the GTV, and normal lung V20Gy. RESULTS: Twelve of 20 plans can be optimized sufficiently with SFO. SFO plans were less sensitive to the interplay effect compared to MFO plans in terms of target coverage for both LPB and LPMB. The following comparisons showed results utilizing the MFO technique. In the interplay evaluation without repainting, the mean V100%RX of the GTV were 99.42 ± 0.6%, 97.52 ± 3.9%, and 94.49 ± 7.3% for CPB, LPB, and LPMB plans, respectively. Following VR (2 × for CPB; 3 × for LPB; 5 × for LPMB), V100%RX of the GTV were improved (on average) by 0.13%, 1.84%, and 4.63%, respectively, achieving the acceptance criteria of V100%RX > 95%. Because of fast energy switch in linear accelerator proton machines, the delivery time for VR plans was the lowest for LPB plans, while delivery time for LPMB was on average 1 min longer than CPB plans. The advantage of small spot machines was better sparing in normal lung V20Gy, even when VR was applied. CONCLUSION: In the absence of repainting, proton machines with large spot sizes generated more robust plans against interplay effects. The number of VR increased with decreasing spot sizes to achieve the acceptance criteria. VR improved the plan robustness against interplay effects for modalities with small spot sizes and fast energy changes, preserving the low dose sparing aspect of the LPMB, even when motion is included.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cyclotrons , Lung Neoplasms , Particle Accelerators , Proton Therapy , Radiosurgery , Radiotherapy Planning, Computer-Assisted , Lung Neoplasms/radiotherapy , Lung Neoplasms/diagnostic imaging , Humans , Radiosurgery/methods , Proton Therapy/methods , Radiotherapy Planning, Computer-Assisted/methods , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Retrospective Studies , Radiotherapy Dosage , Respiration
17.
Med Dosim ; 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38616141

ABSTRACT

High dose rate (HDR) brachytherapy procedures for cervical cancer require multiple applicator insertions for multiple (typically 5) fractions of a single plan, which carries a risk for variability in applicator position between fractions. Due to applicator displacement relative to patient anatomy, the dose to nearby organs-at-risk (OARs) may vary significantly from one fraction to the next. The purpose of this study was to evaluate the effect of changes in HDR tandem and ring (T&R) applicator position on doses to nearby OARs and to present a quick and simple method to estimate doses to OARs inter-fractionally without having to perform a re-plan. Ninety CT image sets for 20 patients, ages 44 to 86, undergoing T&R-based HDR for cervical cancer were used retrospectively for this study. Measures of applicator positional and angular changes relative to the bony anatomy were obtained using image fusion in MIM software, between the planning CT (plan CT) and the CT on the treatment day (CT-TX). Dosimetric data were determined, also using MIM software, using the original (first fraction) dose distribution applied to organs at risk (rectum and bladder), transferred via rigid registration from the plan CT to each CT-TX. Bladder and rectum contours were also transferred from each plan CT to each CT-TX and were tweaked manually to match anatomy on each CT-TX and examined visually for appropriateness. Differences in translation and rotation of the T&R applicator between the planning CT and subsequent individual fractions were recorded and plotted against dose differences between each fraction of treatment and the original (first) fraction. Absolute dose (D2cc) and volume (V50) differences vs positional shifts were calculated and plotted, and the Pearson Product-Moment correlation coefficient between dose parameters and measured positional shifts was determined. Average dosimetric differences between planned dose and subsequent fractional doses obtained through rigid registration were 1.48 ± 1.92 Gy, 14.91 ± 11.92 cm3, 0.56 ± 0.93 Gy, and 1.77 ± 2.18 cm3 for Bladder D2cc, Bladder V50, Rectum D2cc, and Rectum V50, respectively. Correlation between Bladder V50 and sagittal plane rotation gave an r2 of 0.4, showing the most correlation of all parameters studied. Bladder dose and volume increased by a maximum of about 2.7 Gy and 50 cm3 overall for Bladder D2cc and Bladder V50, respectively. Bladder V50 was most sensitive to T&R applicator displacements. We have quantified the effects of applicator positional changes on dose changes for the bladder and rectum. Even large changes in applicator position between fractions did not result in significant changes in dose to these normal tissues, indicating that adaptive re-planning is not necessary.

18.
Chem Sci ; 15(8): 2937-2945, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38404383

ABSTRACT

An efficient method for the late-stage selective O-fluoroalkylation of tyrosine residues with a stable yet highly reactive fluoroalkylating reagent, 3,3-difluoroallyl sulfonium salts (DFASs), has been developed. The reaction proceeds in a mild basic aqueous buffer (pH = 11.6) with high efficiency, high biocompatibility, and excellent regio- and chemoselectivity. Various oligopeptides and phenol-containing bioactive molecules, including carbohydrates and nucleosides, could be selectively O-fluoroalkylated. The added vinyl and other functional groups from DFASs can be valuable linkers for successive modification, significantly expanding the chemical space for further bioconjugation. The synthetic utility of this protocol has been demonstrated by the fluorescently labeled anti-cancer drug and the synthesis of O-link type 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid-tyrosine3-octreotate (DOTA-TATE), showing the prospect of the method in medicinal chemistry and chemical biology.

19.
Int J Retina Vitreous ; 10(1): 1, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38167553

ABSTRACT

BACKGROUND: To evaluate retinal structural and functional changes after silicone oil (SO) removal in eyes with macula-off rhegmatogenous retinal detachment (RRD). METHODS: Best-corrected visual acuity (BCVA) testing, microperimetry, and optical coherence tomography angiography were performed in 48 eyes with macula-off RRD before and 3 months after SO removal. The values of healthy contralateral eyes were used as control data. Correlations between retinal vessel density (VD), retinal nerve fiber layer thickness (RNFLT), the interval between retinal detachment and surgery, the duration of SO tamponade, the follow-up time after SO removal, and visual function were analyzed. RESULTS: Significant increases in 2˚ fixation rate (FR), 4˚ FR, 2˚ mean retinal sensitivity (MRS), 6˚ MRS, parafoveal superficial capillary plexus VD and RNFLT were observed after SO removal (all P < 0.05). The increase of 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade and the follow-up time after SO removal respectively (all P < 0.05). The last 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade, the interval between retinal detachment and surgery, and the follow-up time after SO removal (all P < 0.01). The last FR in RRD eyes was close to that of contralateral eyes (P > 0.05). CONCLUSION: Retinal structure and function improved to different degrees after SO removal. Fixation stability and retinal sensitivity increased more than BCVA postoperatively. Retinal sensitivity, which was affected by the interval between retinal detachment and surgery and the duration of SO tamponade, gradually recovered after SO removal.

20.
J Appl Clin Med Phys ; 25(3): e14284, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38295191

ABSTRACT

PURPOSE: External beam radiotherapy is a complex process, involving timely coordination among multiple teams. The aim of this study is to report our experience of establishing a standardized workflow and using quantitative data and metrics to manage the time-to-treatment initiation (TTI). METHODS AND MATERIALS: Starting in 2014, we established a standard process in a radiation oncology-specific electronic medical record system (RO-EMR) for patients receiving external beam radiation therapy in our department, aiming to measure the time interval from simulation to treatment initiation, defined as TTI, for radiation oncology. TTI data were stratified according to the following treatment techniques: three-dimensional (3D) conformal therapy, intensity-modulated radiotherapy (IMRT), and stereotactic body radiotherapy (SBRT). Statistical analysis was performed with the Mann-Whitney test for the respective metrics of aggregate data for the initial period 2012- 2015 (PI) and the later period 2016-2019 (PII). RESULT: Over 8 years, the average annual number of treatments for PI and PII were 1760 and 2357 respectively, with 3D, IMRT, and SBRT treatments accounting for 53, 29, 18% and 44, 34, 22%, respectively, of the treatment techniques. The median TTI for 3D, IMRT, and SBRT for PI and PII were 1, 6, 7, and 1, 5, 7 days, respectively, while the 90th percentile TTI for the three techniques in both periods were 5, 9, 11 and 4, 9, 10 days, respectively. From the aggregate data, the TTI was significantly reduced (p = 0.0004, p < 0.0001, p < 0.0001) from PI to PII for the three treatment techniques. CONCLUSION: Establishing a standardized workflow and frequently measuring TTI resulted in shortening the TTI during the early years (in PI) and maintaining the established TTI in the subsequent years (in PII).


Subject(s)
Radiosurgery , Radiotherapy, Conformal , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy Planning, Computer-Assisted/methods , Workflow , Radiotherapy, Conformal/methods , Radiotherapy, Intensity-Modulated/methods , Radiosurgery/methods
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