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This work investigates the less conservative stability conditions for linear systems with a time-varying delay. At first, augmented Lyapunov-Krasovskii functionals(LKFs) are constructed with state vectors that have not been utilized in the existing works, and an augmented zero equality that can be derived according to the augmented vector is proposed. By utilizing them, a stability condition is proposed in the form of a linear matrix inequality. And, by using novel delay-dependent LKFs and the introduced ones, improved results are obtained than the previous result. The addition of the delay-dependent LKFs increases the number of decision variables in the results. Therefore, any vectors of integral inequalities utilized in the proposed criterion are appropriately adjusted to reduce computational complexity. To check the excellence and validity of the proposed results, several numerical examples are applied.
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BACKGROUND: To analyze the outcomes of clipping and coiling for ruptured intracranial aneurysms (RIAs) based on data from the National Health Insurance Service in South Korea, with a focus on variations according to region and hospital size. METHODS: This study analyzed the one-year mortality rates for patients with RIAs who underwent clipping or coiling in 2018. Coiling was further categorized into non-stent assisted coiling (NSAC) and stent assisted coiling (SAC). Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs), or semi-general hospitals (sGHs) based on size. South Korea's administrative districts were divided into 15 regions for analysis. RESULTS: In 2018, there were 2,194 (33.1%) clipping procedures (TRGH, 985; GH, 827; sGH, 382) and 4,431 (66.9%) coiling procedures (TRGH, 1,642; GH, 2076; sGH, 713) performed for RIAs treatment. Among hospitals performing more than 20 treatments, the one-year mortality rates following clipping or coiling were 11.2% and 16.0%, respectively, with no significant difference observed. However, there was a significant difference in one-year mortality between NSAC and SAC (14.3% vs. 19.5%, P = 0.034), with clipping also showing significantly lower mortality compared to SAC (P = 0.019). No significant differences in other treatment modalities were observed according to hospital size, but clipping at TRGHs had significantly lower mortality than at GHs (P = 0.042). While no significant correlation was found between the number of treatments and outcomes at GHs, at TRGHs, a higher volume of clipping procedures was significantly associated with lower total mortality (P = 0.023) and mortality after clipping (P = 0.022). CONCLUSION: Using Korea NHIS data, mortality rates for RIAs showed no significant variation by hospital size due to coiling's prevalence. However, differences in clipping outcomes by hospital size and volume in TRGH highlight the need for national efforts to improve clipping skills and standardization. Additionally, the higher mortality rate with SAC emphasizes the importance of precise indications for its application.
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Aneurisma Roto , Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/mortalidade , República da Coreia , Feminino , Pessoa de Meia-Idade , Masculino , Aneurisma Roto/terapia , Aneurisma Roto/mortalidade , Idoso , Resultado do Tratamento , Estudos de Coortes , AdultoRESUMO
Objective: Stents have been widely used for coil embolization for intracranial aneurysms. Few studies have analyzed the risk factors of recanalization through long-term follow-up observation of only stent-assisted coiling. We analyzed the risk factors for recanalization through long-term observations. Methods: A total number of 399 unruptured aneurysms treated by stent-assisted coil embolization between 2003 and 2016 in a single institution were analyzed for determining the factors associated with recanalization including the patient characteristics, aneurysms, and procedural variables. All patients underwent angiographic follow-up with digital subtraction angiography or magnetic resonance angiography at 24 months or more following the procedure. Results: Recanalization occurred in 8%. The mean time for the recanalization was 21.1 ± 14.0 months (range, 5-51 months). The receiver operating characteristic curve analysis indicated areas under the curve for a maximum aneurysm size of 0.773 (cut-off, 6.415 mm). Multivariate analysis revealed that the maximum aneurysm size and parent artery curvature at which the aneurysm developed were significantly associated with recanalization. In parent artery curvature, the bifurcation group (OR, 9.02; 95% CI, 2.53-32.13; p = 0.001) and the convex group (OR, 3.68; 95% CI, 1.17-11.50; p = 0.025) were independent predictors of recanalization compared with the straight group. Conclusion: The maximum aneurysm size and parent artery curvature are risk factors associated with recanalization in stent-assisted coil embolization.
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OBJECTIVE: The aim of this study was to identify predictive factors of postoperative cerebral infarction (PostCI) following combined bypass (CB) surgery in adult patients with moyamoya disease (MMD) using quantitative parameters from the rapid processing of perfusion and diffusion (RAPID) perfusion CT (PCT) software. METHODS: The authors retrospectively reviewed 276 total hemispheres in patients with MMD who underwent CB. Preoperative volumes of time-to-maximum (Tmax) > 4 sec and > 6 sec were obtained from the RAPID analysis of PCT. These quantitative parameters, along with other clinical and angiographic factors, were statistically analyzed to determine the significant predictors for PostCI following CB. RESULTS: PostCI occurred in 17 hemispheres (6.16%). PCA involvement (p = 0.016), and the volume of Tmax > 6 sec (p < 0.001) and Tmax > 4 sec (p < 0.001), were identified as variables related to PostCI in the univariable analysis. In the multivariable analysis, the volume of Tmax > 6 sec (OR 1.013, 95% confidence interval 1.007-1.019, p < 0.001) was determined to be an independent predictive factor significantly associated with PostCI after CB in adult patients with MMD. In the receiver operating characteristic (ROC) curve, the cutoff value of the preoperative volume of Tmax > 6 sec was determined to be 59.5 ml (sensitivity 82.4%, specificity 71.9%, area under the ROC curve 0.811). CONCLUSIONS: For adult patients with MMD and a large volume of Tmax > 6 sec over 59.5 ml, more caution is required when deciding to undergo bypass surgery and in postoperative management.
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OBJECTIVE: To analyze the relationship between in-stent restenosis (ISR) following carotid artery stenting (CAS) and platelet clopidogrel reactivity confirmed by the P2Y12 reaction unit (PRU) and inhibition rate (IR). METHODS: We retrospectively analyzed 171 patients who underwent CAS with extracranial carotid stenosis from January 2016 to December 2019. Dual antiplatelet therapy with 100 mg aspirin and 75 mg clopidogrel was started ≥5 days before CAS. Clopidogrel resistance was measured with the PRU and IR the day before CAS. The ISR degree was classified into R1, R2, and R3 (moderate to severe luminal stenosis of ≥50% or occlusion) by carotid CT angiography after 24-30 months. The degree of quantitative association between platelet reactivity and ISR R3 was determined by the receiver operating characteristic curve method. The optimal cut-off values of PRU and IR were derived using the maximum Youden index. RESULTS: There were 33 R3 degrees of ISR (19.3%) and nine ipsilateral ischemic strokes (5.3%). The PRU and IR were different between R1+R2 degrees (176.4±50.1, 27.5±18.7%) and R3 degree (247.5±55.0, 10.3±13.4%) (P<0.001). The areas under the curves of PRU and IR were 0.841 and 0.781, and the optimal cut-off values were 220.0 and 14.5%, respectively. Multivariate logistic regression analysis showed that PRU ≥220 and IR ≤14.5% were significant predictive factors for ISR R3 (P<0.001 and P=0.017, respectively). ISR R3 was independently associated with ipsilateral ischemic stroke after CAS (P=0.012). CONCLUSIONS: High PRU (≥220) and low IR (≤14.5%) are related to ISR R3 following CAS, which may cause ipsilateral ischemic stroke.
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BACKGROUND: There have been few reports on the preventative value of intensive blood pressure (BP) management for stroke since the American College of Cardiology/American Heart Association (ACC/AHA) announced the new criteria for hypertension (HTN) in 2017. This study aimed to identify optimal BP for prevention of stroke in healthy adults under 65 years. METHODS: We conducted a 10-year observational study on the risk of stroke, subclassified as hemorrhagic stroke (HS) or ischemic stroke (IS), according to BP categories (low-normal BP, high-normal BP, elevated BP, stage 1 HTN, and stage 2 HTN) using the National Health Insurance Service Database. RESULTS: In 2008, a health checkup was conducted for a total of 8,327,751 participants, and 949,551 of them enrolled in this study. The risk of HS increased from stage 2 HTN (adjusted hazard ratio [AHR], 3.036 [95 % confidence interval [CI], 2.159-4.252]) in men to stage 1 HTN (AHR, 2.972; 95 % CI, 2.256-3.897) in women. The risk of IS increased in both men (AHR, 1.404 [95 % CI, 1.164-1.693]) and women (AHR, 2.012 [95 % CI, 1.603-2.526]) with stage 1 HTN. The overall risk of stroke increased in men (AHR, 1.386; [95 % CI, 1.180-1.629]) and women (AHR, 2.363 [95 % CI, 1.973-2.830]) with stage 1 HTN. CONCLUSION: This study underscores the importance of maintaining BP below Stage 1 HTN to prevent stroke in healthy adults aged below 65 years. These findings highlight the significance of the new HTN guidelines established by the ACC/AHA in 2017.
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Hipertensão , Hipotensão , AVC Isquêmico , Acidente Vascular Cerebral , Adulto , Masculino , Estados Unidos , Humanos , Feminino , Pressão Sanguínea , Hipertensão/complicações , Hipertensão/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de RiscoRESUMO
BACKGROUND: Xenotransplantation, particularly when involving pig donors, presents challenges related to the transmission of porcine cytomegalovirus (pCMV) and its potential impact on recipient outcomes. This study aimed to investigate the relationship between pCMV positivity in both donors and recipients and the survival time of cynomolgus monkey recipients after xenogeneic kidney transplantation. METHODS: We conducted 20 cynomolgus xenotransplants using 18 transgenic pigs. On the surgery day, donor pig blood was sampled, and DNA was extracted from serum and peripheral blood mononuclear cells. Recipient DNA extraction followed the same protocol from pre-transplantation to post-transplantation. Porcine cytomegalovirus detection used real-time polymerase chain reaction (real-time PCR) with the ViroReal kit, achieving a sensitivity of 50 copies/reaction. A Ct value of 37.0 was the pCMV positivity threshold. RESULTS: Of 20 cynomolgus recipients, when donors tested negative for pCMV, recipients also showed negative results in 9 cases. In 4 cases where donors were negative, recipients tested positive. All 5 cases with pCMV-positive donors resulted in positive assessments for recipients. Detection of donor pCMV correlated with shorter recipient survival. Continuous recipient positivity during observation correlated with shorter survival, whereas transient detection showed no significant change in survival rates. However, donor pig phenotypes and transplantation protocols did not significantly impact survival. CONCLUSION: The detection of pCMV in both donors and recipients plays a crucial role in xenotransplantation outcomes. These findings suggest the importance of monitoring and managing pCMV in xenotransplantation to enhance long-term outcomes.
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Infecções por Citomegalovirus , Citomegalovirus , Transplante de Rim , Macaca fascicularis , Transplante Heterólogo , Animais , Transplante Heterólogo/efeitos adversos , Suínos , Citomegalovirus/genética , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/virologia , Transplante de Rim/efeitos adversos , Sobrevivência de Enxerto , Doadores de Tecidos , Animais Geneticamente ModificadosRESUMO
Quantum well intermixing (QWI) is an effective method for simple and well-defined monolithic integration of photonic devices. We introduce an identical-active electro-absorption modulated laser (IA-EML) with optimized QWI, which is applied to reduce the absorptive waveguide region. To determine the optimal intermixed IA-EML structure, we conduct a comparative analysis between the cases of an IA-EML with only an intermixed waveguide region and with both intermixed waveguide and electro-absorption modulator (EAM) regions, as well as the case without QWI. The results reveal that the intermixed region effectively inhibits the absorption in the waveguide. In particular, the IA-EML with only waveguide intermixing exhibits superior modulation characteristics with low driving voltages and a high extinction ratio. Our work provides an attractive approach for suppressing the absorptive waveguide region in the IA-EML to enhance modulation performance and to develop photonic integrated circuits with a simplified process.
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An approach for synthesizing AgInZnS/CdS/ZnS core-shell-shell quantum dots (QDs) that demonstrate exceptional stability and electroluminescence (EL) performance is introduced. This approach involves incorporating a cadmium sulfide (CdS) interlayer between an AgInZnS (AIZS) core and a zinc sulfide (ZnS) shell to prevent the diffusion of Zn ions into the AIZS core and the cation exchange at the core-shell interface. Consequently, a uniform and thick ZnS shell, with a thickness of 2.9 nm, is formed, which significantly enhances the stability and increases the photoluminescence quantum yield (87.5%) of the QDs. The potential for AIZS/CdS/ZnS QDs in electroluminescent devices is evaluated, and an external quantum efficiency of 9.6% in the 645 nm is achieved. These findings highlight the importance of uniform and thick ZnS shells in improving the stability and EL performance of QDs.
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Although hypothermic treatment has been reported to have some beneficial effects on ischaemia at the clinical level, the mechanism of ischaemia suppression by hypothermia remains unclear due to a lack of mechanism understanding and insufficient data. The aim of this study was to isolate and characterize microRNAs specifically expressed in ischaemia-hypothermia for the dihydropyrimidinase-like 3 (Dpysl3) gene. PC12 cells were induced with CoCl2 for chemical ischaemia and incubated at 32 â for hypothermia. In ischaemia-hypothermia, four types of microRNAs (miR-106b-5p, miR-194-5p, miR-326-5p, and miR-497-5p) were highly related to the Dpysl3 gene based on exosomal microRNA analysis. Dpysl3 gene expression was up-regulated by miR-497-5p but down-regulated by miR-106b-5p, miR-194-5p and miR-326-5p. Our results suggest that these four microRNAs are involved in the regulation of Dpysl3 gene expression. These findings provide valuable clues that exosomal microRNAs could be used as therapeutic targets for effective treatment of ischaemia.
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Hipotermia , MicroRNAs , Animais , Humanos , Ratos , Expressão Gênica , Hipotermia/genética , Isquemia/induzido quimicamente , Isquemia/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Células PC12RESUMO
Introduction: Since the analgesic effect of acupuncture stimulation is derived from different mechanisms depending on the type of pain, it is important to know which acupuncture points to stimulate. In this study, to confirm the effect of acupuncture stimulation on acute pain from a neurological point of view, somatosensory evoked potential and sensory threshold changes were evaluated to identify the nerve range that is affected by acupuncture stimulation on LI4 (Hapgok acupuncture point, of the radial nerve) during acute pain. Methods: The subjects were 40 healthy men and women aged 19-35 years. The study was designed as a randomly controlled, crossover trial with acupuncture stimulation at LI4 as the intervention. The washout period for acupuncture stimulation was 2 weeks, and the subjects were divided into two groups, i.e., an acupuncture stimulation group and a nonstimulation group, with 10 men and 10 women in each group. Somatosensory evoked potential measurement was carried out for 5 min by alternately applying 2 HZ-pulse electrical stimulation to the thumb and the little finger of the hand acupunctured with a 64-channel electroencephalogram. The verbal rating scale was used before and after each acupuncture stimulation session. Result and discussion: The results of the study confirmed that the somatosensory evoked potential amplitude value of the thumb was significantly decreased and that the intensity of sensory stimulation corresponding to a verbal rating scale score of 6 was significantly increased only in the thumb after acupuncture stimulation. Therefore, the results show that acupuncture treatment for acute pain is more effective when direct acupuncture stimulation is applied to the painful area.
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Upper airway cough syndrome (UACS) is a common cause of chronic cough characterized by upper airway symptoms, including nasal discharge and throat discomfort. Empirical treatments for UASC-induced chronic cough, such as first-generation antihistamines, have been used; however, the long-term use of these medicines has adverse effects. Therefore, we evaluate the efficacy, safety, and economic feasibility of Wolbigachul-tang (WBGCT), an herbal medication for UASC-induced chronic cough. This is a randomized, double-blind, active-comparator-controlled, parallel, and exploratory clinical trial. Thirty patients with UASC-induced chronic cough will be recruited and randomly allocated to the WBGCT and control groups in a 1:1 allocation ratio. The investigational medicine will be administered three times per day for 2 weeks (3 g of WBGCT at a time). The primary outcome measure is the cough symptom score measured at screening, before starting the trial, and after 2 and 4 weeks. Secondary outcome measures include the cough visual analog scale, nasal discharge score, questionnaire of clinical symptoms of cough and sputum, Leicester cough questionnaire-Korean version, integrative medicine outcome scale, integrative medicine patient satisfaction scale, and 5-level EuroQol 5-dimensional questionnaire, which will be assessed before starting the trial and after 2 and 4 weeks. This study aims to investigate the efficacy, safety, and economic feasibility of WBGCT in the treatment of chronic cough. Therefore, the results of this trial provide evidence for the application of WBGCT in the treatment of UACS-induced chronic cough.
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This article scrutinizes the stabilization and fault reconstruction issues for interval type-2 fuzzy-based cyber-physical systems with actuator faults, deception attacks and external disturbances. The primary objective of this research is to formulate the learning observer system with the interval type-2 fuzzy technique that reconstructs the actuator faults as well as the immeasurable states of the addressed fuzzy based model. Further, the information of reconstructed actuator faults is incorporated in the developed controller with the imperfect premise variables for ensuring the stabilization of the system under consideration. At the same time, the H∞ technique is employed to reduce the impact of external disturbances in the considered model. In addition to that, the deception attacks are represented as a stochastic variable that satisfies the Bernoulli distributions. On the ground of this, a set of sufficient criteria is deduced in the context of linear matrix inequalities to affirm the stability of the addressed systems. Furthermore, the requisite gain matrices are computed by resolving the obtained linear matrix inequality based stability criteria. At last, two simulation examples, including the mass-spring-damper system are exhibited to demonstrate the usefulness of analytical findings of the developed strategy.
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Background: There are few reports on the preventative value of intensive blood pressure (BP) management for stroke, especially hemorrhagic stroke (HS), after new criteria for hypertension (HTN) were announced by the American College of Cardiology/American Heart Association in 2017. Aims: This study aimed to identify the optimal BP for the primary prevention of HS in a healthy population aged between 20 and 65 years. Methods: We conducted a 10-year observational study on the risk of HS, subclassified as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) according to BP categories (e.g., low normal BP, high normal BP, elevated BP, stage 1 HTN, and stage 2 HTN) using the National Health Insurance Service Database. Results: Out of 8,327,751 participants who underwent a health checkup in 2008, 949,550 were included in this study and observed from 2009 to 2018. The risk of ICH was significantly increased in men with stage 2 HTN {adjusted hazard ratio [aHR] 2.002 [95% confidence interval (CI) 1.203-3.332]} and in women with stage 1 HTN [aHR 2.021 (95% CI, 1.251-3.263)]. The risk of SAH was significantly increased in both men [aHR 1.637 (95% CI, 1.066-2.514)] and women [aHR 4.217 (95% CI, 2.648-6.715)] with stage 1 HTN. Additionally, the risk of HS was significantly increased in men with stage 2 HTN [aHR 3.034 (95% CI, 2.161-4.260)] and in women with stage 1 HTN [aHR 2.976 (95% CI, 2.222-3.986)]. Conclusion: To prevent primary HS, including ICH and SAH, BP management is recommended for adults under the age of 65 years with stage 1 HTN.
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In the development of new organic crystals for nonlinear optical and terahertz (THz) applications, it is very challenging to achieve the essentially required non-centrosymmetric molecular arrangement. Moreover, the resulting crystal structure is mostly unpredictable due to highly dipolar molecular components with complex functional substituents. In this work, new organic salt crystals with top-level macroscopic optical nonlinearity by controlling the van der Waals volume (VvdW ), rather than by trial and error, are logically designed. When the VvdW of molecular ionic components varies, the corresponding crystal symmetry shows an observable trend: change from centrosymmetric to non-centrosymmetric and back to centrosymmetric. All non-centrosymmetric crystals exhibit an isomorphic P1 crystal structure with an excellent macroscopic second-order nonlinear optical response. Apart from the top-level macroscopic optical nonlinearity, new organic crystals introducing highly electronegative fluorinated substituents with strong secondary bonding ability show excellent performance in efficient and broadband THz wave generation, high crystal density, high thermal stability, and good bulk crystal growth ability.
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OBJECTIVE: To analyze the outcomes of coil embolization (CE) for unruptured intracranial aneurysm (UIA) according to region and hospital size based on National Health Insurance Service data in South Korea. METHODS: The incidence of complications, including intracranial hemorrhage (ICRH) and cerebral infarction (CI), occurring within 3 months and the 1-year mortality rates in UIA patients who underwent CE in 2018 were analyzed. Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs) or semigeneral hospitals (sGHs) according to their size, and the administrative districts of South Korea were divided into 15 regions. RESULTS: In 2018, 8425 (TRGHs, 4438; GHs, 3617; sGHs, 370) CEs were performed for UIAs. Complications occurred in 5.69% of patients seen at TRGHs, 13.48% at GHs, and 20.45% at sGHs. The complication rate in TRGHs was significantly lower than that in GHs (p=0.039) or sGHs (p=0.005), and that in GHs was significantly lower than that in sGHs (p=0.030). The mortality rates in TRGHs, GHs, and sGHs were 0.81%, 2.16%, and 3.92%, respectively, with no significant difference. Despite no significant difference in the mortality rates, the complication rate significantly increased as the number of CE procedures per hospital decreased (p=0.001; rho=-0.635). Among the hospitals where more than 30 CEs were performed for UIAs, the incidence of CIs (p=0.096, rho=-0.205) and the mortality rates (3 months, p=0.048, rho=-0.243; 1 year, p=0.009, rho=-0.315) significantly decreased as the number of CEs that were performed increased and no significant difference in the incidence of post-CE ICRH was observed. CONCLUSION: The complication rate in patients who underwent CE for UIA increased as the hospital size and physicians' experience in conducting CEs decreased. We recommend nationwide quality control policies CEs for UIAs.
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ABSTRACT: BACKGROUND: Patients with unruptured intracranial aneurysms (UIAs) treated by coil embolization may experience illness uncertainty despite successful treatment. This study aimed to investigate illness uncertainty in patients with UIAs treated by coil embolization and to identify the factors affecting illness uncertainty. METHODS: This cross-sectional study involved data collected from 267 patients with UIAs who received coil embolization within 2 years at a tertiary hospital in South Korea. The data were collected through structured questionnaires and the patients' medical records. The questionnaires included information on sociodemographic characteristics, the Hospital Anxiety and Depression Scale, the Multidimensional Scale of Perceived Social Support, and Mishel Uncertainty in Illness Scale data. We collected clinical characteristics through the medical records. Data analysis was performed using descriptive statistics, an independent t test, a 1-way analysis of variance, and a Pearson correlation test. We used a multiple linear regression analysis with significant variables in the univariate analysis to determine which variables had a significant impact on illness uncertainty. RESULTS: The mean Mishel Uncertainty in Illness Scale score was 52.33 (12.93). We identified age ( P = .002), education level (high school graduation, P = .014; college or higher, P < .001), anxiety ( P < .001), and social support ( P < .001) as factors affecting illness uncertainty. CONCLUSION: Patients with UIAs who underwent coil embolization did not exhibit severe illness uncertainty. The factors affecting illness uncertainty were age, educational level, anxiety, and social support. This study provides insight into illness uncertainty in this patient population and may help develop appropriate nursing interventions.
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Rose (Rosa hybrida) is a major flower crop worldwide and has long been loved for its variety of colors and scents. Roses are mainly used for gardening or cutting flowers and are also used as raw materials for perfumes, cosmetics, and food. Essential oils, which are extracted from the flowers of plants, including roses, have various scents, and the essential oil market has been growing steadily owing to the growing awareness of the benefits of natural and organic products. Therefore, it is necessary to develop a system that stably supplies raw materials with uniform ingredients in line with the continuous increase in demand. In this study, conditions for the efficient induction of callus were established from the petals of the rose breeding line 15R-12-2, which has a strong scent developed by the National Institute of Horticultural and Herbal Science, Rural Development Administration. The highest callus induction rate (65%) was observed when the petals of the fully open flower (FOF) were placed on the SH11DP medium so that the abaxial surface was in contact with the medium. In addition, the VOCs contained in the petals of 15R-12-2 and the petal-derived callus were analyzed by HS-SPME-GC-MS. Thirty components, including esters and alcohols, were detected in the petal-derived callus. Among them, 2-ethylhexan-1-ol, which showed 59.01% relative content when extracted with hexane as a solvent, was the same component as detected in petals. Therefore, petal-derived callus is expected to be of high industrial value and can be suggested as an alternative pathway to obtaining VOCs.
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BACKGROUND: the objective of this study is to evaluate the predictive power of the survival model using deep learning of diffusion-weighted images (DWI) in patients with non-small-cell lung cancer (NSCLC). METHODS: DWI at b-values of 0, 100, and 700 sec/mm2 (DWI0, DWI100, DWI700) were preoperatively obtained for 100 NSCLC patients who underwent curative surgery (57 men, 43 women; mean age, 62 years). The ADC0-100 (perfusion-sensitive ADC), ADC100-700 (perfusion-insensitive ADC), ADC0-100-700, and demographic features were collected as input data and 5-year survival was collected as output data. Our survival model adopted transfer learning from a pre-trained VGG-16 network, whereby the softmax layer was replaced with the binary classification layer for the prediction of 5-year survival. Three channels of input data were selected in combination out of DWIs and ADC images and their accuracies and AUCs were compared for the best performance during 10-fold cross validation. RESULTS: 66 patients survived, and 34 patients died. The predictive performance was the best in the following combination: DWI0-ADC0-100-ADC0-100-700 (accuracy: 92%; AUC: 0.904). This was followed by DWI0-DWI700-ADC0-100-700, DWI0-DWI100-DWI700, and DWI0-DWI0-DWI0 (accuracy: 91%, 81%, 76%; AUC: 0.889, 0.763, 0.711, respectively). Survival prediction models trained with ADC performed significantly better than the one trained with DWI only (p-values < 0.05). The survival prediction was improved when demographic features were added to the model with only DWIs, but the benefit of clinical information was not prominent when added to the best performing model using both DWI and ADC. CONCLUSIONS: Deep learning may play a role in the survival prediction of lung cancer. The performance of learning can be enhanced by inputting precedented, proven functional parameters of the ADC instead of the original data of DWIs only.
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Advanced ovarian cancer currently has few therapeutic options. Poly(ADP-ribose) polymerase (PARP) inhibitors bind to nuclear PARP and trap the protein-inhibitor complex to DNA. This work investigates a theranostic PARP inhibitor for targeted radiopharmaceutical therapy of ovarian cancer in vitro and PET imaging of healthy mice in vivo. METHODS: [77Br]RD1 was synthesized and assessed for pharmacokinetics and cytotoxicity in human and murine ovarian cancer cell lines. [76Br]RD1 biodistribution and organ uptake in healthy mice were quantified through longitudinal PET/CT imaging and ex vivo radioactivity measurements. Organ-level dosimetry following [76/77Br]RD1 administration was calculated using RAPID, an in-house platform for absorbed dose in mice, and OLINDA for equivalent and effective dose in human. RESULTS: The maximum specific binding (Bmax), equilibrium dissociation constant (Kd), and nonspecific binding slope (NS) were calculated for each cell line. These values were used to calculate the cell specific activity uptake for cell viability studies. The half maximal effective concentration (EC50) was measured as 0.17 (95 % CI: 0.13-0.24) nM and 0.46 (0.13-0.24) nM for PARP(+) and PARP(-) expressing cell lines, respectively. The EC50 was 0.27 (0.21-0.36) nM and 0.30 (0.22-0.41) nM for BRCA1(-) and BRCA1(+) expressing cell lines, respectively. When measuring the EC50 as a function of cellular activity uptake and nuclear dose, the EC50 ranges from 0.020 to 0.039 Bq/cell and 3.3-9.2 Gy, respectively. Excretion through the hepatobiliary and renal pathways were observed in mice, with liver uptake of 2.3 ± 0.4 %ID/g after 48 h, contributing to estimated absorbed dose values in mice of 19.3 ± 0.3 mGy/MBq and 290 ± 10 mGy/MBq for [77Br]RD1 and [76Br]RD1, respectively. CONCLUSION: [77Br]RD1 cytotoxicity was dependent on PARP expression and independent of BRCA1 status. The in vitro results suggest that [77Br]RD1 cytotoxicity is driven by the targeted Meitner-Auger electron (MAe) radiotherapeutic effect of the agent. Further studies investigating the theranostic potential, organ dose, and tumor uptake of [76/77Br]RD1 are warranted.