Establishment and validation of a risk score model based on EUS: assessment of lymph node metastasis in early gastric cancer.

BACKGROUND AND AIMS: Lymph node metastasis significantly affects the prognosis of early gastric cancer patients. EUS plays a crucial role in the preoperative assessment of early gastric cancer. This study evaluated the efficacy of EUS in identifying lymph node metastasis in early gastric cancer patients and developed a risk score model to aid in choosing the best treatment options. METHODS: We retrospectively analyzed the effectiveness of EUS for detecting lymph node metastasis in early gastric cancer patients. A risk score model for predicting lymph node metastasis preoperatively was created using independent risk factors identified through binary logistic regression analysis and subsequently validated. Receiver operating characteristic curves were generated for both the development and validation cohorts. RESULTS: The overall accuracy of EUS in identifying lymph node metastasis was 85.3%, although its sensitivity (29.2%) and positive predictive value (38.7%) were relatively low. Patients were categorized based on preoperative risk factors for lymph node metastasis, including tumor size of ≥20 mm, lymph nodes of ≥10 mm, body mass index of ≥24 kg/m2, and lymph node metastasis on CT scans. A 7-point risk score model was developed to assess the likelihood of lymph node metastasis. The areas under the receiver operating characteristic curve for the development and validation sets were 0.842 and 0.837, respectively, with sensitivities of 64% and 79%, respectively. CONCLUSIONS: We developed a practical risk score model based on preoperative factors to help EUS predict lymph node metastasis in early gastric cancer patients, guiding the selection of optimal treatment approaches for these patients.

Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome.

INTRODUCTION: Neuroblastoma is the most common extracranial solid tumor in children. Patients with high-risk neuroblastoma have a 5-year survival rate less than 50% after extensive treatment. Signaling pathways control cell fate decisions that dictate the behavior of tumor cells. The deregulation of signaling pathways is etiological in cancer cells. Thus, we speculated that the pathway activity of neuroblastoma contains more prognostic information and therapeutic targets. METHODS: Using a footprint-based method, we calculated the activity of fourteen pathways in neuroblastoma. Through stepwise Cox regression analyses, we established a three-gene prognostic signature whose predictive performance was evaluated by external validation. Combining a single-cell sequencing dataset, the most active pathways in high-risk neuroblastoma were found. RESULTS: We found that several pathway activities were correlated with neuroblastoma outcomes. We built a three-gene model comprising DLK1, FLT3, and NTRK1, which exhibited superior internal and external performances. We created a nomogram that combines clinical characteristics to aid in the selection and visualization of high-risk neuroblastoma patients. Furthermore, by integrating a single-cell sequencing dataset, we found that estrogen and MAPK were the most active pathways in high-risk neuroblastoma. CONCLUSION: Our findings suggest that pathway-related therapies may hold promise for the treatment of high-risk neuroblastoma.

Feasibility study of deep learning-based markerless real-time lung tumor tracking with orthogonal X-ray projection images.

PURPOSE: The feasibility of a deep learning-based markerless real-time tumor tracking (RTTT) method was retrospectively studied with orthogonal kV X-ray images and clinical tracking records acquired during lung cancer treatment. METHODS: Ten patients with lung cancer treated with marker-implanted RTTT were included. The prescription dose was 50 Gy in four fractions, using seven- to nine-port non-coplanar static beams. This corresponds to 14-18 X-ray tube angles for an orthogonal X-ray imaging system rotating with the gantry. All patients underwent 10 respiratory phases four-dimensional computed tomography. After a data augmentation approach, for each X-ray tube angle of a patient, 2250 digitally reconstructed radiograph (DRR) images with gross tumor volume (GTV) contour labeled were obtained. These images were adopted to train the patient and X-ray tube angle-specific GTV contour prediction model. During the testing, the model trained with DRR images predicted GTV contour on X-ray projection images acquired during treatment. The predicted three-dimensional (3D) positions of the GTV were calculated based on the centroids of the contours in the orthogonal images. The 3D positions of GTV determined by the marker-implanted RTTT during the treatment were considered as the ground truth. The 3D deviations between the prediction and the ground truth were calculated to evaluate the performance of the model. RESULTS: The median GTV volume and motion range were 7.42 (range, 1.18-25.74) cm3 and 22 (range, 11-28) mm, respectively. In total, 8993 3D position comparisons were included. The mean calculation time was 85 ms per image. The overall median value of the 3D deviation was 2.27 (interquartile range: 1.66-2.95) mm. The probability of the 3D deviation smaller than 5 mm was 93.6%. CONCLUSIONS: The evaluation results and calculation efficiency show the proposed deep learning-based markerless RTTT method may be feasible for patients with lung cancer.

A virtual audit system for intensity-modulated radiation therapy credentialing in Japan Clinical Oncology Group clinical trials: A pilot study.

PURPOSE: The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data. METHODS: We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2). RESULTS: The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively. CONCLUSION: This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system.

Influences of women empowerment indices on demand for childcare services: Evidence from the Nigeria Demographic and Health Surveys.

This study examined the effect of various dimensions of women's empowerment on childcare use in Nigeria, utilizing information from five rounds of the National Demographic and Health Surveys. The analysis made use of both binary and multinomial logistic regression. The findings show that women who share household choices with their spouses were more likely to undertake postnatal care for their babies in either private or public hospitals compared to self-medication/others/traditional. Also, women who owned houses and those who participate in economic activities are significantly more inclined to use postnatal services for babies in health facilities. By implication, women empowerment is a significant factor to consider in improving childcare services in Nigeria. This suggests that in order to improve the health of children, women's inputs in household decision-making should be accommodated, while efforts should be made to enhance household socioeconomic position, and support mothers to have formal education. The findings also suggest that promoting women's empowerment can play a crucial role in increasing the demand for formal childcare services.

Cette étude a examiné l'effet de diverses dimensions de l'autonomisation des femmes sur le recours aux services de garde d'enfants au Nigéria, en utilisant les informations provenant de cinq séries d'enquêtes nationales sur la démographie et la santé. L'analyse a fait appel à la régression logistique binaire et multinomiale. Les résultats montrent que les femmes qui partagent les choix de ménage avec leur conjoint étaient plus susceptibles d'entreprendre des soins postnatals pour leur bébé dans des hôpitaux privés ou publics que par l'automédication/autres/traditionnels. En outre, les femmes qui possèdent une maison et celles qui participent à des activités économiques sont beaucoup plus enclines à recourir aux services postnatals pour les bébés dans les établissements de santé. Par conséquent, l'autonomisation des femmes est un facteur important à prendre en compte dans l'amélioration des services de garde d'enfants au Nigeria. Cela suggère que pour améliorer la santé des enfants, la contribution des femmes à la prise de décision au sein du ménage doit être prise en compte, tandis que des efforts doivent être déployés pour améliorer la position socioéconomique du ménage et aider les mères à suivre une éducation formelle. Les résultats suggèrent également que la promotion de l'autonomisation des femmes peut jouer un rôle crucial dans l'augmentation de la demande de services formels de garde d'enfants.

Do health expenditures affect under-five mortality and life expectancy in the ECOWAS sub-Region?

This research explored the effect of health expenditures on health outcomes in the Economic Community of West African States (ECOWAS). The study employed panel data from 2001 to 2020 of all ECOWAS member States (15 countries) and tested the datasets for the presence of a unit root after the descriptive statistics analysis had been carried out. Based on the result of the Augmented Dickey-Fuller stationarity test, the Fully Modified Ordinary Least Squares (FMOLS) method was applied. The result showed that public health expenditure was statistically significant and indirectly related to life expectancy. On the other hand, public health expenditure, private health expenditure and external health expenditure were significantly related with infant mortality. Public health expenditure was found to be directly related to infant mortality while private health and external health expenditures were negatively related. In the light of the above findings, it is recommended that policymakers in the ECOWAS region should devote a higher proportion of their annual budgets to healthcare as a strategy to improve health outcomes, reduce under-five mortality rates, and increase life expectancy in the region.

Cette recherche a exploré l'effet des dépenses de santé sur les résultats de santé dans la Communauté économique des États de l'Afrique de l'Ouest (CEDEAO). L'étude a utilisé des données de panel de 2001 à 2020 de tous les États membres de la CEDEAO (15 pays) et a testé les ensembles de données pour la présence d'une racine unitaire après la réalisation de l'analyse statistique descriptive. Sur la base du résultat du test de stationnarité augmentée de Dickey-Fuller, la méthode des moindres carrés ordinaires entièrement modifiés (FMOLS) a été appliquée. Le résultat a montré que les dépenses publiques de santé étaient statistiquement significatives et indirectement liées à l'espérance de vie. En revanche, les dépenses de santé publique, les dépenses de santé privées et les dépenses de santé externes étaient significativement liées à la mortalité infantile. Il a été constaté que les dépenses de santé publique étaient directement liées à la mortalité infantile, tandis que les dépenses de santé privées et les dépenses de santé externes étaient négativement liées. À la lumière des conclusions ci-dessus, il est recommandé que les décideurs politiques de la région de la CEDEAO consacrent une plus grande proportion de leurs budgets annuels aux soins de santé en tant que stratégie visant à améliorer les résultats sanitaires, à réduire les taux de mortalité des moins de cinq ans et à augmenter l'espérance de vie dans la région.

The molecular mechanism of a novel derivative of BTO-956 induced apoptosis in human myelomonocytic lymphoma cells.

Acute myeloid leukemia (AML) is a malignant cancer of the hematopoietic system. Although the effectiveness of arsenic compounds has been recognized and applied clinically, some patients are still found resistant to this chemotherapy. In this study, we investigated that a synthetic thyroid hormone analog (TA), 2-iodo-4-nitro-1-(o-tolyloxy) benzene, had a strong apoptosis effect on U937 cells. U937 cells were treated with TA, and examinted the generation of reactive oxygen species (ROS), dysfunction of mitochondria, expression of pro-apoptosis and anti-apoptosis, and cleavage of caspase-3 and Poly (ADP-ribose) polymerase (PARP). Further, it is also evaluated that insight molecular mechanism and signaling pathways involved in the study. It is found that TA significantly induced apoptosis in U937 cells through production of ROS, dysfunction of mitochondria, and activation of caspase cascade. It was also observed that MAPK signaling pathway including ERK, JNK, and P38 signals are involved in the induction of apoptosis. Moreover, marked activation of autophagy and ER stress markers such as LC3, P62, Beclin1 and GRP78, CHOP were observed, respectively. Pretreatment with ER stress inhibitor tauroursodeoxycholic acid (TUDCA) and autophagy inhibitor 3-Methyladenine (3-MA) have successfully attenuated and aggravated TA-induced apoptosis, respectively. We further confirmed the active involvement of ER stress and autophagy signals. In conclusion, TA induced apoptosis through ER stress and activation of autophagy, and the latter is not conducive to TA-induced cell death. Our results may provide a new insight into the strategic development of novel therapy for the treatment of AML.

Safety and Feasibility of Radiotherapy Plus Camrelizumab for Locally Advanced Esophageal Squamous Cell Carcinoma.

LESSONS LEARNED: Radiotherapy plus anti-PD-1 antibody as first-line therapy is safe and feasible in locally advanced esophageal squamous cell carcinoma (ESCC). Tumor-infiltrating and peripheral lymphocytes were associated with patient survival. Further studies combining chemoradiotherapy with immunotherapy in locally advanced ESCC and exploration of predictive biomarkers are warranted. BACKGROUND: We conducted a phase Ib study of radiotherapy plus programmed cell death protein 1 (PD-1) monoclonal antibody camrelizumab as first-line treatment for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: We planned to enroll 20 patients with newly diagnosed locally advanced ESCC. Patients received 60 Gy radiation (2.0 Gy/fraction, 5 fractions/week), with camrelizumab (200 mg every 2 weeks) starting with radiotherapy and continuing for 32 weeks (i.e., for 16 cycles). The primary endpoints were safety and feasibility. Secondary endpoints were rates of radiologic and pathologic response, overall survival (OS), and progression-free survival (PFS). Study data were collected by the week during radiotherapy (RT), every month during the maintenance camrelizumab treatment, and every 3 months after treatment. Tumor microenvironment and peripheral blood were monitored at baseline and after 40 Gy radiation for association with efficacy. RESULTS: Twenty patients were enrolled and received treatment. One patient (patient 10) was excluded upon discovery of a second tumor in the bladder during treatment, leaving 19 patients for analysis. Toxicity was deemed tolerable. Fourteen (74%) patients had assessed objective response. At a median follow-up time of 31.0 months (95% confidence interval [CI], 27.0-35.1), median OS and PFS times were 16.7 months (95% CI, 5.9-27.9) and 11.7 months (95% CI, 0-30.3), respectively. OS and PFS rates at 24 months were 31.6% and 35.5%, respectively. Kaplan-Meier analysis revealed associations between the following factors and OS/PFS: tumor programmed cell death ligand 1 (PD-L1) expression, PD-1+ CD8+ , PD-1+ CD4+ T cells, and PD-L1+ CD4+ T cells; peripheral blood CD4+ , CD8+ , CD4+ regulatory T cells, and their subsets. CONCLUSION: Radiotherapy plus camrelizumab had manageable toxicity and antitumor efficacy for locally advanced ESCC. Several biomarkers were associated with clinical benefit and deserve further study.

Rapid identification of chemical compositions in callicarpa kwangtungensis Chun by ultra-high-performance liquid chromatography with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry.

Callicarpa kwangtungensis Chun is a traditional Chinese medicine that has various therapeutic effects. Despite its wide use in Chinese medicine, the study is still quite limited, especially its chemical compositions. In this research, an ultra-high-pressure liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry tandem mass spectrometry method was utilized to analyze its chemical compositions for the first time. As a result, a total of 124 compounds, including 20 phenylethanoid glycosides, 31 flavonoids, 36 organic acids, 26 terpenoids and 11 phenols, were identified or tentatively characterized in 30 min. Among them, 49 compounds, including 5 phenylethanoid glycosides, 12 flavonoids, 16 organic acids, 12 terpenoids, and 4 phenols, were identified in Callicarpa kwangtungensis Chun for the first time. Besides, the fragmentation pathways were also discussed. This research established a rapid and reliable method to analyze the chemical compositions of complicated herb without the process of isolation, and provide abundant information on the chemical material basis for further bioactivity and quality control studies.

Protective effect of dihydromyricetin on hyperthermia-induced apoptosis in human myelomonocytic lymphoma cells.

Dihydromyricetin (DMY) is a traditional herbal medicine, with a wide range of biological activities. Extreme hyperthermia (HT) can suppress the immune system; thus, protection of the immune system is beneficial in heat-related diseases, including heatstroke. In our study, we revealed the protective effect of DMY against HT-induced apoptosis and analysed the underlying molecular mechanisms. We incubated human myelomonocytic lymphoma U937 cells at 44 °C for 30 min with or without DMY and followed by further incubation for 6 h at 37 °C. Cell viability was determined by the CCK-8 assay. DMY did not cause any cytotoxic effects in U937 cells even at high doses. HT treatment alone induced significant apoptosis, which was detected by DNA fragmentation and Annexin V/PI double staining. Mitochondrial dysfunction was identified by loss of mitochondrial membrane potential (MMP) during heat stimulation. Apoptotic related proteins were involved, truncated Bid and caspase-3 were upregulated, and Mcl-1 and XIAP were downregulated. We also identified the related signalling pathways, such as the MAPK and PI3K/AKT pathways. However, changes in HT were dramatically reversed when the cells were pretreated with DMY before exposure to HT. Overall, MAPKs and PI3K/AKT signalling, mitochondrial dysfunction, and caspase-mediated pathways were involved in the protective effect of DMY against HT-induced apoptosis in U937 cells, which was totally reversed by DMY pretreatment. These findings indicate a new clinical therapeutic strategy for the protection of immune cells during heatstroke.

Three New Abietane-Type Diterpenoids from Callicarpa macrophylla Vahl.

Three new abietane-type diterpenoids, named callicapoic acid M3 (1), callicapoic acid M4 (2) and callicapoic acid M5 (3), were isolated from the Callicarpa macrophylla Vahl. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). All the isolated three compounds were evaluated for inhibitory activity on NO production in LPS-activated RAW 264.7 macrophage cells by using MTT assays. Compounds 1, 2 and 3 showed potent inhibitory activity, with inhibition rates of 34.47-40.13%.

Assessing the impact of international trade on ecological footprint in Belt and Road Initiative countries.

The Belt and Road Initiative (BRI) is one such comprehensive plan that aims to boost economic growth and connectivity across Africa, Asia, and Europe. While the effort may be good for boosting exports and foreign direct investment (FDI), some are worried about the toll it may take on the environment. Therefore, we aim to examine the effect of international trade and FDI on the ecological footprint in BRI countries, considering the mediating role of the environmental performance index. The CCEMG estimator was used to examine the impacts of imports, exports, FDI, population growth, urbanization, and the Environmental Performance Index (EPI) on the global ecological footprint. Our findings show that export has a positive relationship with ecological footprint. Similarly, imports and FDI revealed a positive association with the ecological footprint. Finally, environmental performance revealed a negative association with ecological footprint in BRI countries. Our findings support the pollution haven theory by demonstrating the critical importance of environmental regulations in enticing responsible investors. By using the ecological footprint as an all-encompassing measure of environmental effect, this study sheds light on the need to incorporate sustainability within the goals of the BRI. This research emphasizes the importance of adopting well-informed methods to promote sustainable development and mitigate the BRI's adverse environmental impacts.

The impact of Chinese investment on access to clean and sustainable energy in Africa.

The objective of this study is to examine the relationship between Chinese investment and access to clean and sustainable energy in African countries. We are motivated by the increasing engagement between China and Africa and the priority of sustainable energy for both partners. We employ robust econometric modelling, including fixed effects and the two-step Generalized Method of Moments, on a panel sample of 43 African countries over 19 years. The results show that Chinese energy investment in Africa is significantly associated with increased access to sustainable electricity. This effect is more pronounced in resource-rich countries, suggesting that China is more attracted to these countries due to the opportunities for resource trade in the form of partnerships. The policy implication of this finding is that it highlights the importance of African governments developing favourable strategies and policies to attract more Chinese investments in the energy sector.

Automatic planning for functional lung avoidance radiotherapy based on function-guided beam angle selection and plan optimization.

Objective.This study aims to develop a fully automatic planning framework for functional lung avoidance radiotherapy (AP-FLART).Approach.The AP-FLART integrates a dosimetric score-based beam angle selection method and a meta-optimization-based plan optimization method, both of which incorporate lung function information to guide dose redirection from high functional lung (HFL) to low functional lung (LFL). It is applicable to both contour-based FLART (cFLART) and voxel-based FLART (vFLART) optimization options. A cohort of 18 lung cancer patient cases underwent planning-CT and SPECT perfusion scans were collected. AP-FLART was applied to generate conventional RT (ConvRT), cFLART, and vFLART plans for all cases. We compared automatic against manual ConvRT plans as well as automatic ConvRT against FLART plans, to evaluate the effectiveness of AP-FLART. Ablation studies were performed to evaluate the contribution of function-guided beam angle selection and plan optimization to dose redirection.Main results.Automatic ConvRT plans generated by AP-FLART exhibited similar quality compared to manual counterparts. Furthermore, compared to automatic ConvRT plans, HFL mean dose,V20, andV5were significantly reduced by 1.13 Gy (p< .001), 2.01% (p< .001), and 6.66% (p< .001) respectively for cFLART plans. Besides, vFLART plans showed a decrease in lung functionally weighted mean dose by 0.64 Gy (p< .01),fV20by 0.90% (p= 0.099), andfV5by 5.07% (p< .01) respectively. Though inferior conformity was observed, all dose constraints were well satisfied. The ablation study results indicated that both function-guided beam angle selection and plan optimization significantly contributed to dose redirection.Significance.AP-FLART can effectively redirect doses from HFL to LFL without severely degrading conventional dose metrics, producing high-quality FLART plans. It has the potential to advance the research and clinical application of FLART by providing labor-free, consistent, and high-quality plans.

Allogeneic Hematopoietic Stem Cell Transplantation Can Improve Prognosis of Extramedullary Infiltration Positive t(8;21) Acute Myeloid Leukemia.

BACKGROUND In t(8;21) acute myeloid leukemia (AML), patients with extramedullary infiltration (EMI) tend to have worse survival outcomes than those without EMI. However, it is still unclear whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefits EMI-positive t(8;21) AML patients. MATERIAL AND METHODS This study retrospectively enrolled 651 t(8;21) AML patients, and analyzed 51 patients with EMI at diagnosis. Among the 51 patients, 15 patients received allo-HSCT. RESULTS The incidence of EMI in t(8;21) AML was 10.0%, and the first complete remission rate was 78.5% in EMI-positive t(8;21) AML patients. The central nervous system was the most frequently involved site (29.4%), followed by bones (15.7%), and skin (9.8%). In terms of karyotype, 19 (37.3%) patients were t(8;21) alone, 12 (23.5%) had additional loss of a sex chromosome, and 5 (9.8%) had complex karyotype. Significantly better overall survival was observed in patients with allo-HSCT compared to patients without allo-HSCT in both multivariable models (HR=0.32; P=0.0122) and the Kaplan-Meier curves (P=0.0157). CONCLUSIONS Allo-HSCT improved the survival of EMI-positive t(8;21) AML.

Validation of the YuWell YE660D oscillometric upper-arm blood pressure monitor for clinic and home in general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization Universal Standard (International Organization for Standardization 81060-2:2018) and the International Organization for Standardization Amendment 1. 2020.

OBJECTIVE: To evaluate the accuracy of the YuWell YE660D oscillometric upper-arm blood pressure (BP) monitor in general population (for clinic and home BP measurements in adults) according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2 : 2018) and its Amendment 1. 2020. METHODS: Subjects were recruited to fulfill the age, sex, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method. Two cuffs of the test device were used for arm circumferences 22-32 cm (standard) and 22-45 cm (wide range). RESULTS: Ninety-two subjects were recruited and 85 subjects were analyzed. For validation criterion 1, the mean ±â€…SD of the differences between the test device and reference BP readings was 0.3 ±â€…7.2/2.2 ±â€…5.5 mmHg (systolic/diastolic). For validation criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 6.1/4.8 mmHg (systolic/diastolic). CONCLUSION: The YuWell YE660D oscillometric upper-arm electronic BP monitor has passed the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2 : 2018) and its Amendment 1. 2020 in adults and hence can be recommended for home and clinical use.

Development of independent dose verification plugin using Eclipse scripting API for brachytherapy.

In this study, an independent dose verification plugin (DVP) using the Eclipse Scripting Application Programming Interface (ESAPI) for brachytherapy was developed. The DVP was based on the general 2D formalism reported in AAPM-TG43U1. The coordinate and orientation of each source position were extracted from the translation matrix acquired from the treatment planning system (TPS), and the distance between the source and verification point (r) was calculated. Moreover, the angles subtended by the center-tip and tip-tip of the hypothetical line source with respect to the verification point (θ and ß) were calculated. With r, θ, ß and the active length of the source acquired from the TPS, the geometry function was calculated. As the TPS calculated the radial dose function, g(r), and 2D anisotropy function, F(r,θ), by interpolating and extrapolating the corresponding table stored in the TPS, the DVP calculated g(r) and F(r,θ) independently from equations fitted with the Monte Carlo data. The relative deviation of the fitted g(r) and F(r,θ) for the GammaMed Plus HDR 192Ir source was 0.5% and 0.9%, respectively. The acceptance range of the relative dose difference was set to ±1.03% based on the relative deviation between the fitted functions and Monte Carlo data, and the linear error propagation law. For 64 verification points from sixteen plans, the mean of absolute values of the relative dose difference was 0.19%. The standard deviation (SD) of the relative dose difference was 0.17%. The DVP maximizes efficiency and minimizes human error for the brachytherapy plan check.

Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer.

Dormant cancer cells account for cancer recurrence, distant metastasis and drug resistance which lead to poor prognosis in colorectal cancer (CRC). However, little is known about the molecular mechanisms regulating tumor cell dormancy and how to eliminate dormant cancer cells. Recent studies indicate autophagy affects dormant tumor cell survival. Here, we found that polo-like kinases 4 (PLK4), a central regulator of the cell cycle and proliferation, plays a crucial role in regulating CRC cells dormancy both in vitro and in vivo. Downregulation of PLK4 induced dormancy and inhibited migration and invasion in different CRC cell lines. Clinically, PLK4 expression was correlated with the dormancy markers (Ki67, p-ERK, p-p38) and late recurrence in CRC tissues. Mechanistically, downregulation of PLK4 induced autophagy contributed to restoring phenotypically aggressive tumor cells to a dormant state through the MAPK signaling pathway, and inhibition of autophagy would trigger apoptosis of dormant cells. Our findings reveal that downregulation of PLK4-induced autophagy contributes to tumor dormancy and autophagy inhibition leads to apoptosis of CRC dormant cells. Our study is the first to report that downregulation PLK4 induced autophagy is an early event in CRC dormancy and highlights autophagy inhibitor as a potential therapeutic target for dormant cell elimination.

Development of a deep learning-based patient-specific target contour prediction model for markerless tumor positioning.

PURPOSE: For pancreatic cancer patients, image guided radiation therapy and real-time tumor tracking (RTTT) techniques can deliver radiation to the target accurately. Currently, for the radiation therapy machine with kV X-ray imaging systems, internal markers must be implemented to facilitate tumor tracking. The purpose of this study was to develop a markerless deep learning-based pancreatic tumor positioning procedure for real-time tumor tracking with a kV X-ray imaging system. METHODS AND MATERIALS: Fourteen pancreatic cancer patients treated with intensity-modulated radiation therapy from six fixed gantry angles with a gimbal-head radiotherapy system were included in this study. For a gimbal-head radiotherapy system, the three-dimensional (3D) intrafraction target position can be determined using an orthogonal kV X-ray imaging system. All patients underwent four-dimensional computed tomography (4DCT) simulations for treatment planning, which were divided into 10 respiratory phases. After a patient's 4DCT was acquired, for each X-ray tube angle, 10 digitally reconstructed radiograph (DRR) images were obtained. Then, a data augmentation procedure was conducted. The data augmentation procedure first rotated the CT volume around the superior-inferior and anterior-posterior directions from -3° to 3° in 1.5° intervals. Then, the Super-SloMo model was adapted to interpolate 10 frames between respiratory phases. In total, the data augmentation procedure expanded the data scale 250-fold. In this study, for each patient, 12 datasets containing the DRR images from each specific X-ray tube angle based on the radiation therapy plan were obtained. The augmented dataset was randomly divided into training and testing datasets. The training dataset contained 2000 DRR images with clinical target volume (CTV) contours labeled for fine-tuning the pre-trained target contour prediction model. After the fine-tuning, the patient and X-ray tube angle-specific CTV contour prediction model was acquired. The testing dataset contained the remaining 500 images to evaluate the performance of the CTV contour prediction model. The dice similarity coefficient (DSC) between the area enclosed by the CTV contour and predicted contour was calculated to evaluate the model's contour prediction performance. The 3D position of the CTV was calculated based on the centroid of the contour in the orthogonal DRR images, and the 3D error of the prediction position was calculated to evaluate the CTV positioning performance. For each patient, the DSC results from 12 X-ray tube angles and 3D error from 6 gantry angles were calculated, representing the novelty of this study. RESULTS: The mean and standard deviation (SD) of all patients' DSCs were 0.98 and 0.015, respectively. The mean and SD of the 3D error were 0.29 mm and 0.14 mm, respectively. The global maximum 3D error was 1.66 mm, and the global minimum DSC was 0.81. The mean calculation time for CTV contour prediction was 55 ms per image. This fulfills the requirement of RTTT. CONCLUSIONS: Regarding the positioning accuracy and calculation efficiency, the presented procedure can provide a solution for markerless real-time tumor tracking for pancreatic cancer patients.

Endoscopic ultrasound-guided fine needle aspiration for smooth benign appearing malignant esophageal stricture: a cross-sectional study.

Background: Endoscopic biopsy is standard for the diagnosis of esophageal malignancy. However, few cases are difficult to diagnose as they present with smooth esophageal stricture with negative biopsy results. We aimed to evaluate the effectiveness and safety of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of biopsy-negative suspected malignant esophageal strictures. Methods: We retrospectively analyzed cases of esophageal stricture with negative biopsies. From September 2016 to November 2021, 50 patients were enrolled. All the patients accepted the EUS-FNA examination. And histological and cytological specimens were obtained from all patients. Clinical, endoscopic, imaging, cytological, and histopathological results were noted and analyzed. Results: A total of 50 patients (40 male and 10 female) were enrolled in this study. The 19G puncture needle was used in 6 cases and the 22G puncture needle was used in 44 cases; an average of 2.7 needles were used per case. Satisfactory specimens were obtained by EUS-FNA for all subjects. All patients were diagnosed as malignant tumor. The diagnosis was confirmed by EUS-FNA biopsies in 98% of patients. Based on the surgical pathology results, there were 16 cases of esophageal squamous cell carcinoma, 2 cases of esophageal metastatic carcinoma, 1 case of esophageal sarcoma, 22 cases of lung cancer, 6 cases of mediastinal lymph node metastasis, and 3 cases of mediastinal tumor. No obvious complications were observed. A total of 5 cases were treated with surgery, 28 with chemotherapy, 3 with chemotherapy + surgery, and 12 with radiotherapy; 2 patients ceased treatment. No obvious complications, such as bleeding and mediastinal infection, were observed. Conclusions: EUS-FNA is effective and safe for the diagnosis of malignant esophageal strictures with smooth overlying esophageal mucosa. EUS-FNA is effective and safe for patients with smooth esophagus stenosis for whom satisfactory cytological and histological specimens can be obtained, and the diagnosis can be confirmed by cytological, histological, and immunohistochemical examinations. It can be used as the first choice for diagnosis and treatment.