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1.
Inorg Chem ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949263

ABSTRACT

The single-step purification of ethylene (C2H4) from a mixture of carbon dioxide (CO2), acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) was achieved through MOF Compound-1, where the aromatic pore surface and carboxylates selectively recognized C2H6 and CO2, respectively, resulting in a reversal of the adsorption orders for both gases (C2H6 > C2H4 and CO2 > C2H4). Breakthrough testing verified that the C2H4 purification ability could be enhanced 2.6 times after adding impure CO2. Grand Canonical Monte Carlo (GCMC) simulations demonstrate that there are interactions between CO2 and C2H6 molecules as well as between CO2 molecules themselves. These interactions contribute to the enhancement of the C2H4 purification ability upon the addition of CO2 and the increased adsorption of CO2.

2.
Chaos ; 34(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949531

ABSTRACT

Higher-order interactions exist widely in mobile populations and are extremely important in spreading epidemics, such as influenza. However, research on high-order interaction modeling of mobile crowds and the propagation dynamics above is still insufficient. Therefore, this study attempts to model and simulate higher-order interactions among mobile populations and explore their impact on epidemic transmission. This study simulated the spread of the epidemic in a spatial high-order network based on agent-based model modeling. It explored its propagation dynamics and the impact of spatial characteristics on it. Meanwhile, we construct state-specific rate equations based on the uniform mixing assumption for further analysis. We found that hysteresis loops are an inherent feature of high-order networks in this space under specific scenarios. The evolution curve roughly presents three different states with the initial value change, showing different levels of the endemic balance of low, medium, and high, respectively. Similarly, network snapshots and parameter diagrams also indicate these three types of equilibrium states. Populations in space naturally form components of different sizes and isolations, and higher initial seeds generate higher-order interactions in this spatial network, leading to higher infection densities. This phenomenon emphasizes the impact of high-order interactions and high-order infection rates in propagation. In addition, crowd density and movement speed act as protective and inhibitory factors for epidemic transmission, respectively, and depending on the degree of movement weaken or enhance the effect of hysteresis loops.


Subject(s)
Epidemics , Humans , Influenza, Human/epidemiology , Influenza, Human/transmission , Computer Simulation
3.
ACS Macro Lett ; : 874-881, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949618

ABSTRACT

The frequent mutations of influenza A virus (IAV) have led to an urgent need for the development of innovative antiviral drugs. Glycopolymers offer significant advantages in biomedical applications owing to their biocompatibility and structural diversity. However, the primary challenge lies in the design and synthesis of well-defined glycopolymers to precisely control their biological functionalities. In this study, functional glycopolymers with sulfated fucose and 6'-sialyllactose were successfully synthesized through ring-opening metathesis polymerization and a postmodification strategy. The optimized heteropolymer exhibited simultaneous targeting of hemagglutinin and neuraminidase on the surface of IAV, as evidenced by MU-NANA assay and hemagglutination inhibition data. Antiviral experiments demonstrated that the glycopolymer displayed broad and efficient inhibitory activity against wild-type and mutant strains of H1N1 and H3N2 subtypes in vitro, thereby establishing its potential as a dual-targeted inhibitor for combating IAV resistance.

4.
J Cardiothorac Surg ; 19(1): 412, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956617

ABSTRACT

BACKGROUND: This study evaluated the prevalence and quantity of lymph nodes at particular stations of the mediastinum in patients with lung cancer. These data are important to radiologists, pathologists, and thoracic surgeons because they can serve as a benchmark when assessing the completeness of lymph node dissection. However, relevant data in the literature are scarce. METHODS: Data regarding the number of lymph nodes derived from two randomised trials of bilateral mediastinal lymph node dissection, the BML-1 and BML-2 study, were included in this analysis. Detectable nodes at particular stations of the mediastinum and the number of nodes at these stations were analysed. RESULTS: The mean number of removed nodes was 28.67 (range, 4-88). Detectable lymph nodes were present at stations 2R, 4R, and 7 in 93%, 98%, and 99% of patients, respectively. Nodes were rarely present at stations 9 L (33%), and 3 (35%). The largest number of nodes was observed at stations 7 and 4R (mean, 5 nodes). CONCLUSION: The number of mediastinal lymph nodes in patients with lung cancer may be greater than that in healthy individuals. Lymph nodes were observed at stations 2R, 4R, and 7 in more than 90% of patients with lung cancer. The largest number of nodes was observed at stations 4R and 7. Detectable nodes were rarely observed at stations 3 and 9 L. TRIAL REGISTRATION: ISRCTN 86,637,908.


Subject(s)
Lung Neoplasms , Lymph Node Excision , Lymph Nodes , Mediastinum , Humans , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Mediastinum/pathology , Lymph Node Excision/methods , Lymph Nodes/pathology , Lymph Nodes/surgery , Male , Female , Aged , Middle Aged , Lymphatic Metastasis , Prevalence
5.
J Cell Mol Med ; 28(13): e18520, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38958523

ABSTRACT

Lung adenocarcinoma (LUAD) is a tumour characterized by high tumour heterogeneity. Although there are numerous prognostic and immunotherapeutic options available for LUAD, there is a dearth of precise, individualized treatment plans. We integrated mRNA, lncRNA, microRNA, methylation and mutation data from the TCGA database for LUAD. Utilizing ten clustering algorithms, we identified stable multi-omics consensus clusters (MOCs). These data were then amalgamated with ten machine learning approaches to develop a robust model capable of reliably identifying patient prognosis and predicting immunotherapy outcomes. Through ten clustering algorithms, two prognostically relevant MOCs were identified, with MOC2 showing more favourable outcomes. We subsequently constructed a MOCs-associated machine learning model (MOCM) based on eight MOCs-specific hub genes. Patients characterized by a lower MOCM score exhibited better overall survival and responses to immunotherapy. These findings were consistent across multiple datasets, and compared to many previously published LUAD biomarkers, our MOCM score demonstrated superior predictive performance. Notably, the low MOCM group was more inclined towards 'hot' tumours, characterized by higher levels of immune cell infiltration. Intriguingly, a significant positive correlation between GJB3 and the MOCM score (R = 0.77, p < 0.01) was discovered. Further experiments confirmed that GJB3 significantly enhances LUAD proliferation, invasion and migration, indicating its potential as a key target for LUAD treatment. Our developed MOCM score accurately predicts the prognosis of LUAD patients and identifies potential beneficiaries of immunotherapy, offering broad clinical applicability.


Subject(s)
Adenocarcinoma of Lung , Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Immunotherapy , Lung Neoplasms , Machine Learning , Humans , Immunotherapy/methods , Prognosis , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/therapy , Biomarkers, Tumor/genetics , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Gene Expression Profiling , MicroRNAs/genetics , Multiomics
6.
Front Microbiol ; 15: 1418959, 2024.
Article in English | MEDLINE | ID: mdl-38962124

ABSTRACT

In recent years, porcine diarrhea-associated viruses have caused significant economic losses globally. These viruses present similar clinical symptoms, such as watery diarrhea, dehydration, and vomiting. Co-infections with porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are common. For the rapid and on-site preliminary diagnosis on the pig farms, this study aimed to develop a colloidal gold immunochromatography assay (GICA) strip for the detection of PEDV and TGEV simultaneously. The GICA kit showed that there was no cross-reactivity with the other five common porcine viruses. With visual observation, the lower limits were approximately 104 TCID50/mL and 104 TCID50/mL for PEDV and TGEV, respectively. The GICA strip could be stored at 4°C or 25°C for 12 months without affecting its efficacy. To validate the GICA strip, 121 clinical samples were tested. The positive rates of PEDV and TGEV were 42.9 and 9.9%, respectively, and the co-infection rate of the two viruses was 5.8% based on the duplex GICA strip. Thus, the established GICA strip is a rapid, specific, and stable tool for on-site preliminary diagnosis of PEDV- and TGEV-associated diarrhea.

7.
Org Lett ; 26(27): 5625-5629, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38953484

ABSTRACT

A palladium-catalyzed cascade carbonylation reaction of 2-bromo-N-(2-iodophenyl)benzamides with benzylidenecyclopropanes for the synthesis of fused isoindolinone derivatives has been developed. A broad range of 6/5/6/6 tetracyclic isoindolinone products were efficiently prepared in moderate to good yields with diverse substitution. Two carbonyl groups were incorporated into the substrates in a single step with the formation of four carbon-carbon bonds and two carbon-heteroatom bonds.

8.
Chemosphere ; 363: 142740, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971442

ABSTRACT

Removal of organic micropollutants (OMPs) from water, especially hydrophilic and ionized ones, is challenging for water remediation. Herein, porous ß-cyclodextrin polymers (PCPs) with tailored functionalization were prepared based on molecular expansion strategy and sulfonation. Partially benzylated ß-cyclodextrin was knotted by external crosslinker to form PCP1, and knotting PCP1 by expansion molecule generated PCP2. PCP1 and PCP2 were sulfonated to achieve PCP1-SO3H and PCP2-SO3H. Based on systematical adsorption evaluation toward multiple categories of OMPs, it was found that the introduced strong polar -SO3H group could bring strong hydrogen bonding and electrostatic interactions. PCP2 showed the highest surface (998.97 m2/g) displayed more excellent adsorption performance toward neutral and anionic OMPs, and the adsorption mechanism for this property of PCP2 was dominated by hydrophobic interactions. In addition, the PCP1-SO3H with the lowest surface area (39.75 m2/g) rather than PCP2-SO3H with higher surface (519.28 m2/g) exhibited more superior adsorption towards hydrophilic and cationic OMPs, benefiting by hydrogen bonding and electrostatic interactions as well as appropriate porosity. These results not only confirmed the performance enhancement of PCPs through the integration of novel preparation strategy, but also provided fundamental guidance for PCPs design for water remediation.

9.
BMC Geriatr ; 24(1): 585, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977983

ABSTRACT

BACKGROUND: The management of preoperative blood glucose levels in reducing the incidence of postoperative delirium (POD) remains controversial. This study aims to investigate the impact of preoperative persistent hyperglycemia on POD in geriatric patients with hip fractures. METHODS: This retrospective cohort study analyzed medical records of patients who underwent hip fracture surgery at a tertiary medical institution between January 2013 and November 2023. Patients were categorized based on preoperative hyperglycemia (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification of hyperglycemia, and percentile thresholds. Multivariate logistic regression and propensity score matching analysis (PSM) were employed to assess the association between different levels of preoperative glucose and POD. Subgroup analysis was conducted to explore potential interactions. RESULTS: A total of 1440 patients were included in this study, with an incidence rate of POD at 19.1% (275/1440). Utilizing multiple logistic analysis, we found that patients with hyperglycemia had a 1.65-fold increased risk of experiencing POD compared to those with normal preoperative glucose levels (95% CI: 1.17-2.32). Moreover, a significant upward trend was discerned in both the strength of association and the predicted probability of POD with higher preoperative glucose levels. PSM did not alter this trend, even after meticulous adjustments for potential confounding factors. Additionally, when treating preoperative glucose levels as a continuous variable, we observed a 6% increase in the risk of POD (95% CI: 1-12%) with each 1mmol/L elevation in preoperative glucose levels. CONCLUSIONS: There exists a clear linear dose-response relationship between preoperative blood glucose levels and the risk of POD. Higher preoperative hyperglycemia was associated with a greater risk of POD. CLINICAL TRIAL NUMBER: NCT06473324.


Subject(s)
Delirium , Hip Fractures , Hyperglycemia , Postoperative Complications , Humans , Hip Fractures/surgery , Hip Fractures/blood , Hyperglycemia/epidemiology , Hyperglycemia/blood , Female , Male , Retrospective Studies , Aged , Aged, 80 and over , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/blood , Delirium/blood , Delirium/epidemiology , Delirium/diagnosis , Delirium/etiology , Blood Glucose/metabolism , Blood Glucose/analysis , Preoperative Period , Incidence , Risk Factors , Propensity Score
10.
NPJ Parkinsons Dis ; 10(1): 130, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982064

ABSTRACT

The metabolic profile predating the onset of Parkinson's disease (PD) remains unclear. We aim to investigate the metabolites associated with incident and prevalent PD and their predictive values in the UK Biobank participants with metabolomics and genetic data at the baseline. A panel of 249 metabolites was quantified using a nuclear magnetic resonance analytical platform. PD was ascertained by self-reported history, hospital admission records and death registers. Cox proportional hazard models and logistic regression models were used to investigate the associations between metabolites and incident and prevalent PD, respectively. Area under receiver operating characteristics curves (AUC) were used to estimate the predictive values of models for future PD. Among 109,790 participants without PD at the baseline, 639 (0.58%) individuals developed PD after one year from the baseline during a median follow-up period of 12.2 years. Sixty-eight metabolites were associated with incident PD at nominal significance (P < 0.05), spanning lipids, lipid constituent of lipoprotein subclasses and ratios of lipid constituents. After multiple testing corrections (P < 9 × 10-4), polyunsaturated fatty acids (PUFA) and omega-6 fatty acids remained significantly associated with incident PD, and PUFA was shared by incident and prevalent PD. Additionally, 14 metabolites were exclusively associated with prevalent PD, including amino acids, fatty acids, several lipoprotein subclasses and ratios of lipids. Adding these metabolites to the conventional risk factors yielded a comparable predictive performance to the risk-factor-based model (AUC = 0.766 vs AUC = 0.768, P = 0.145). Our findings suggested metabolic profiles provided additional knowledge to understand different pathways related to PD before and after its onset.

11.
Nat Commun ; 15(1): 5751, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982071

ABSTRACT

Oxygen vacancy (Ov) is an anionic defect widely existed in metal oxide lattice, as exemplified by CeO2, TiO2, and ZnO. As Ov can modify the band structure of solid, it improves the physicochemical properties such as the semiconducting performance and catalytic behaviours. We report here a new type of Ov as an intrinsic part of a perfect crystalline surface. Such non-defect Ov stems from the irregular hexagonal sawtooth-shaped structure in the (111) plane of trivalent rare earth oxides (RE2O3). The materials with such intrinsic Ov structure exhibit excellent performance in ammonia decomposition reaction with surface Ru active sites. Extremely high H2 formation rate has been achieved at ~1 wt% of Ru loading over Sm2O3, Y2O3 and Gd2O3 surface, which is 1.5-20 times higher than reported values in the literature. The discovery of intrinsic Ov suggests great potentials of applying RE oxides in heterogeneous catalysis and surface chemistry.

12.
World J Gastrointest Surg ; 16(6): 1609-1617, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983327

ABSTRACT

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is a surgical procedure for treating pancreatic cancer; however, the risk of complications remains high owing to the wide range of organs involved during the surgery and the difficulty of anastomosis. Pancreatic fistula (PF) is a major complication that not only increases the risk of postoperative infection and abdominal hemorrhage but may also cause multi-organ failure, which is a serious threat to the patient's life. This study hypothesized the risk factors for PF after LPD. AIM: To identify the risk factors for PF after laparoscopic pancreatoduodenectomy in patients with pancreatic cancer. METHODS: We retrospectively analyzed the data of 201 patients admitted to the Fudan University Shanghai Cancer Center between August 2022 and August 2023 who underwent LPD for pancreatic cancer. On the basis of the PF's incidence (grades B and C), patients were categorized into the PF (n = 15) and non-PF groups (n = 186). Differences in general data, preoperative laboratory indicators, and surgery-related factors between the two groups were compared and analyzed using multifactorial logistic regression and receiver-operating characteristic (ROC) curve analyses. RESULTS: The proportions of males, combined hypertension, soft pancreatic texture, and pancreatic duct diameter ≤ 3 mm; surgery time; body mass index (BMI); and amylase (Am) level in the drainage fluid on the first postoperative day (Am > 1069 U/L) were greater in the PF group than in the non-PF group (P < 0.05), whereas the preoperative monocyte count in the PF group was lower than that in the non-PF group (all P < 0.05). The logistic regression analysis revealed that BMI > 24.91 kg/m² [odds ratio (OR) =13.978, 95% confidence interval (CI): 1.886-103.581], hypertension (OR = 8.484, 95%CI: 1.22-58.994), soft pancreatic texture (OR = 42.015, 95%CI: 5.698-309.782), and operation time > 414 min (OR = 15.41, 95%CI: 1.63-145.674) were risk factors for the development of PF after LPD for pancreatic cancer (all P < 0.05). The areas under the ROC curve for BMI, hypertension, soft pancreatic texture, and time prediction of PF surgery were 0.655, 0.661, 0.873, and 0.758, respectively. CONCLUSION: BMI (> 24.91 kg/m²), hypertension, soft pancreatic texture, and operation time (> 414 min) are considered to be the risk factors for postoperative PF.

13.
World J Diabetes ; 15(6): 1367-1373, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38983816

ABSTRACT

This article is a comprehensive study based on research on the connection between diabetes mellitus (DM) and prostate cancer (PCa). It investigates the potential role of DM as an independent risk factor for PCa, delving into the biological links, including insulin resistance and hormonal changes. The paper critically analyzes previous studies that have shown varying results and introduces mendelian randomization as a method for establishing causality. It emphasizes the importance of early DM screening and lifestyle modifications in preventing PCa, and proposes future research directions for further under-standing the DM - PCa relationship.

14.
Front Neurol ; 15: 1408360, 2024.
Article in English | MEDLINE | ID: mdl-38984037

ABSTRACT

Objective: This study aimed to evaluate the efficacy and safety of buccal acupuncture on postoperative analgesia, perioperative stress response and adverse events in elderly patients undergoing laparoscopic radical gastrectomy. Methods: It was a prospective, outcome assessor-blinded, randomized controlled trial, involving 90 patients aged 65-80 years who were treated with an elective laparoscopic radical gastrectomy. They were randomly assigned to buccal acupuncture group (Group B) and control group (Group C). Buccal acupuncture was applied to patients of Group B before the induction of general anesthesia, while no additional application was given to those in Group C. Patient-controlled intravenous analgesia (PCIA) with sufentanil was postoperatively performed in both groups. Sufentanil consumption and the Visual Analog Scale (VAS) score within 48 h postoperatively were assessed as primary outcomes. Secondary outcomes included peripheral levels of stress markers, intraoperative consumptions of anesthetic drugs and postoperative recovery. Results: Patients in Group B presented significantly lower VAS scores within 24 h and less consumption of sufentanil within 48 h postoperatively (both p < 0.01). The awaking time, time to extubation and length of stay were significantly shorter in Group B than in Group C (p = 0.005, 0.001 and 0.028, respectively). Compared with Group C, stress response and inflammatory response within 24 h postoperatively were also significantly milder in Group B. Conclusion: The use of buccal acupuncture before general anesthesia induction favors the postoperative analgesic effect and recovery in elderly patients undergoing laparoscopic radical gastrectomy, the mechanism of which involves relieving postoperative stress response and inflammatory response. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn) on 15/06/2023 (ChiCTR2300072500).

15.
Eur J Med Chem ; 275: 116645, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38959730

ABSTRACT

Hypoxia-inducible factor 2α (HIF-2α) is a critical transcription factor that regulates cellular responses under hypoxic conditions. In situations of insufficient oxygen supply or patients with Von Hippel-Lindau (VHL) mutations, HIF-2α accumulates and forms a heterodimeric complex with aryl hydrocarbon receptor nuclear translocator (ARNT, or HIF-ß). This complex further binds to coactivator p300 and interacts with hypoxia response elements (HREs) on the DNA of downstream target genes, regulating the transcription of a variety of genes (e.g. VEGFA, CCND1, CXCR4, SLC2A1, etc) involved in various processes like angiogenesis, mitochondrial metabolism, cell proliferation, and metastasis. Targeting HIF-2α holds great promise for effectively addressing solid tumors associated with aberrant oxygen-sensing pathways and hypoxia mechanisms, offering broad application prospects. In this review, we provide an overview of recent advancements (2009-2024) in HIF-2α modulators such as inhibitors, agonists, and degraders for cancer therapy. Additionally, we discuss in detail the challenges and future directions regarding HIF-2α modulators.


Subject(s)
Antineoplastic Agents , Basic Helix-Loop-Helix Transcription Factors , Drug Development , Animals , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Basic Helix-Loop-Helix Transcription Factors/agonists , Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors , Basic Helix-Loop-Helix Transcription Factors/metabolism , Molecular Structure , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology
16.
J Headache Pain ; 25(1): 110, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977951

ABSTRACT

BACKGROUND: New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. METHODS: This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson's correlation analysis between the NODDI indicators and clinical characteristics. RESULTS: Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. CONCLUSIONS: Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.


Subject(s)
Diffusion Tensor Imaging , Gray Matter , White Matter , Humans , White Matter/diagnostic imaging , White Matter/pathology , Female , Gray Matter/diagnostic imaging , Gray Matter/pathology , Male , Adult , Middle Aged , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Headache Disorders/diagnostic imaging , Headache Disorders/pathology , Neurites/pathology
17.
Radiat Oncol ; 19(1): 88, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978062

ABSTRACT

PURPOSE: This study aimed to develop an automated Tomotherapy (TOMO) planning method for cervical cancer treatment, and to validate its feasibility and effectiveness. MATERIALS AND METHODS: The study enrolled 30 cervical cancer patients treated with TOMO at our center. Utilizing scripting and Python environment within the RayStation (RaySearch Labs, Sweden) treatment planning system (TPS), we developed automated planning methods for TOMO and volumetric modulated arc therapy (VMAT) techniques. The clinical manual TOMO (M-TOMO) plans for the 30 patients were re-optimized using automated planning scripts for both TOMO and VMAT, creating automated TOMO (A-TOMO) and automated VMAT (A-VMAT) plans. We compared A-TOMO with M-TOMO and A-VMAT plans. The primary evaluated relevant dosimetric parameters and treatment plan efficiency were assessed using the two-sided Wilcoxon signed-rank test for statistical analysis, with a P-value < 0.05 indicating statistical significance. RESULTS: A-TOMO plans maintained similar target dose uniformity compared to M-TOMO plans, with improvements in target conformity and faster dose drop-off outside the target, and demonstrated significant statistical differences (P+ < 0.01). A-TOMO plans also significantly outperformed M-TOMO plans in reducing V50Gy, V40Gy and Dmean for the bladder and rectum, as well as Dmean for the bowel bag, femoral heads, and kidneys (all P+ < 0.05). Additionally, A-TOMO plans demonstrated better consistency in plan quality. Furthermore, the quality of A-TOMO plans was comparable to or superior than A-VMAT plans. In terms of efficiency, A-TOMO significantly reduced the time required for treatment planning to approximately 20 min. CONCLUSION: We have successfully developed an A-TOMO planning method for cervical cancer. Compared to M-TOMO plans, A-TOMO plans improved target conformity and reduced radiation dose to OARs. Additionally, the quality of A-TOMO plans was on par with or surpasses that of A-VMAT plans. The A-TOMO planning method significantly improved the efficiency of treatment planning.


Subject(s)
Organs at Risk , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/radiotherapy , Female , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Organs at Risk/radiation effects
18.
bioRxiv ; 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38979161

ABSTRACT

When cells in a primary tumor work together to invade into nearby tissue, this can lead to cell dissociations-cancer cells breaking off from the invading front-leading to metastasis. What controls the dissociation of cells, and whether they break off singly or in small groups? Can this be determined by cell-cell adhesion or chemotactic cues given to cells? We develop a physical model for this question, based on experiments that mimic aspects of cancer cell invasion using microfluidic devices with microchannels of different widths. Experimentally, most dissociation events ("ruptures") involve single cells breaking off, but we observe some ruptures of large groups ( ∼ 20 cells) in wider channels. The rupture probability is nearly independent of channel width. We recapitulate the experimental results with a phase field cell motility model by introducing three different cell states (follower, guided, and high-motility metabolically active leader cells) based on their spatial position. These leader cells may explain why single-cell rupture is the universal most probable outcome. Our simulation results show that cell-channel adhesion is necessary for cells in narrow channels to invade, and strong cell-cell adhesion leads to fewer but larger ruptures. Chemotaxis also influences the rupture behavior: Strong chemotaxis strength leads to larger and faster ruptures. Finally, we study the relationship between biological jamming transitions and cell dissociations. Our results suggest unjamming is necessary but not sufficient to create ruptures.

20.
J Gene Med ; 26(7): e3719, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38979878

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with significant variability in prognosis among patients. Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key focus in the area of cancer research. However, the molecular mechanisms of RAC1 in HCC remain incompletely elucidated. MATERIALS AND METHODS: In this study, bioinformatics analysis was used, and public databases were used to obtain information about HCC cases. The samples were categorized into two groups of high and low expression based on the expression level of RAC1 gene. The limma package was used to calculate the differentially expressed genes between the two groups, and univariate Cox regression analysis was used to screen the prognostic related factors. Consensus clustering analysis was performed using the ConsensusClusterPlus package to identify molecular subtypes of HCC patients. Immune cell infiltration and ESTIMATE scores were assessed using the single sample gene set enrichment analysis and ESTIMATE algorithms. The sensitivity of different isoforms to chemotherapeutic agents was predicted by the oncoPredict package. Finally, we also performed cell function experiments to validate the biological role of RAC1 in vitro. Initially, we classified patients into high and low expression groups based on RAC1 gene expression levels and identified 195 up-regulated genes and 107 down-regulated genes. Through univariate Cox regression analysis, we screened out 169 prognosis-related factors. Furthermore, HCC patients were categorized into two subtypes. Subsequently, Kaplan-Meier survival curves showed that there was a significant difference in prognosis between the two molecular subtypes. Further analysis indicated substantial differences in gene expression levels and TIDE scores between two molecular subtypes. Moreover, these two subtypes exhibited varying sensitivity to chemotherapy drugs, as evidenced by differences in IC50 values. In addition, we found that the silence of RAC1 could effectively inhibit the migration and invasion of HCC cells in vitro. CONCLUSION: This study sheds light on the molecular intricacies of RAC1 in HCC and identifies patient populations that may benefit from immunotherapeutic interventions, with potential implications for tailored treatment strategies.


Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular , Computational Biology , Gene Expression Regulation, Neoplastic , Liver Neoplasms , rac1 GTP-Binding Protein , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/mortality , rac1 GTP-Binding Protein/genetics , rac1 GTP-Binding Protein/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/immunology , Liver Neoplasms/mortality , Prognosis , Computational Biology/methods , Biomarkers, Tumor/genetics , Gene Expression Profiling , Cell Line, Tumor , Kaplan-Meier Estimate
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